Input: Congenital hypothyroidism due to a new deletion in the sodium / iodide symporter protein . OBJECTIVE : Iodide transport defect ( ITD ) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells , that often results in congenital hypothyroidism . When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium / iodide symporter ( NIS ) . PATIENT : We describe a woman with hypothyroidism identified at the 3rd month of life . The diagnosis of ITD was suspected because of nodular goitre , and little if any iodide uptake by the thyroid and salivary glands . Treatment with iodide partially corrected the hypothyroidism ; however , long - term substitution therapy with L - thyroxine was started . MEASUREMENTS : Thyroid radioiodide uptake was only 1 . 4 % and 0 . 3 % at 1 and 24 h after the administration of recombinant human TSH . The saliva to plasma I - ratio was 1 . 1 indicating that the inability of the thyroid gland to concentrate I - was also present in the salivary glands . RESULTS : Analysis of the patient ' s NIS gene revealed a 15 nucleotide ( nt ) deletion of the coding sequence ( nt 1314 through nt 1328 ) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron . The patient was homozygous for this insertion / deletion , while both consanguineous parents were heterozygous . This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI ( 439 - 443 ) which are located in the 6th intracellular loop . COS - 7 cells transfected with a vector expressing the mutant del - ( 439 - 443 ) NIS failed to concentrate iodide , suggesting that the mutation was the direct cause of the ITD in this patient . CONCLUSION : In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene .

Congenital hypothyroidism

Iodide transport defect

ITD

inability of the thyroid

congenital hypothyroidism

hypothyroidism

ITD

nodular goitre

hypothyroidism

ITD

congenital hypothyroidism

sodium / iodide symporter

sodium / iodide symporter

NIS

TSH

NIS

NIS

NIS

iodide

iodide

iodide

L - thyroxine

radioiodide

I -

I -

iodide

PATIENT

woman

human

patient

patient

patient

deletion of the coding sequence ( nt 1314 through nt 1328 )

insertion of 15 nt duplicating the first 15

lacking the five terminal amino acids of exon XI ( 439 - 443 )

del - ( 439 - 443 )

COS - 7

deletion of the coding sequence ( nt 1314 through nt 1328 )

Congenital hypothyroidism

deletion of the coding sequence ( nt 1314 through nt 1328 )

congenital hypothyroidism

deletion of the coding sequence ( nt 1314 through nt 1328 )

congenital hypothyroidism

lacking the five terminal amino acids of exon XI ( 439 - 443 )

Iodide transport defect

lacking the five terminal amino acids of exon XI ( 439 - 443 )

ITD

lacking the five terminal amino acids of exon XI ( 439 - 443 )

ITD

lacking the five terminal amino acids of exon XI ( 439 - 443 )

ITD

del - ( 439 - 443 )

Iodide transport defect

del - ( 439 - 443 )

ITD

del - ( 439 - 443 )

ITD

del - ( 439 - 443 )

ITD

lacking the five terminal amino acids of exon XI ( 439 - 443 )

Congenital hypothyroidism

lacking the five terminal amino acids of exon XI ( 439 - 443 )

congenital hypothyroidism

lacking the five terminal amino acids of exon XI ( 439 - 443 )

congenital hypothyroidism

del - ( 439 - 443 )

Congenital hypothyroidism

del - ( 439 - 443 )

congenital hypothyroidism

del - ( 439 - 443 )

congenital hypothyroidism

Congenital hypothyroidism

insertion of 15 nt duplicating the first 15

congenital hypothyroidism

insertion of 15 nt duplicating the first 15

congenital hypothyroidism

insertion of 15 nt duplicating the first 15

inability of the thyroid

iodide

inability of the thyroid

iodide

inability of the thyroid

iodide

inability of the thyroid

radioiodide

inability of the thyroid

I -

inability of the thyroid

I -

inability of the thyroid

iodide

Iodide transport defect

iodide

Iodide transport defect

iodide

Iodide transport defect

iodide

Iodide transport defect

radioiodide

Iodide transport defect

I -

Iodide transport defect

I -

Iodide transport defect

iodide

ITD

iodide

ITD

iodide

ITD

iodide

ITD

radioiodide

ITD

I -

ITD

I -

ITD

iodide

ITD

iodide

ITD

iodide

ITD

iodide

ITD

radioiodide

ITD

I -

ITD

I -

ITD

iodide

ITD

iodide

ITD

iodide

ITD

iodide

ITD

radioiodide

ITD

I -

ITD

I -

ITD

iodide

iodide

sodium / iodide symporter

iodide

sodium / iodide symporter

iodide

NIS

iodide

NIS

iodide

NIS

iodide

NIS

iodide

sodium / iodide symporter

iodide

sodium / iodide symporter

iodide

NIS

iodide

NIS

iodide

NIS

iodide

NIS

iodide

sodium / iodide symporter

iodide

sodium / iodide symporter

iodide

NIS

iodide

NIS

iodide

NIS

iodide

NIS

radioiodide

sodium / iodide symporter

radioiodide

sodium / iodide symporter

radioiodide

NIS

radioiodide

NIS

radioiodide

NIS

radioiodide

NIS

I -

sodium / iodide symporter

I -

sodium / iodide symporter

I -

NIS

I -

NIS

I -

NIS

I -

NIS

I -

sodium / iodide symporter

I -

sodium / iodide symporter

I -

NIS

I -

NIS

I -

NIS

I -

NIS

iodide

sodium / iodide symporter

iodide

sodium / iodide symporter

iodide

NIS

iodide

NIS

iodide

NIS

iodide

NIS

Congenital hypothyroidism

sodium / iodide symporter

Congenital hypothyroidism

sodium / iodide symporter

Congenital hypothyroidism

NIS

Congenital hypothyroidism

NIS

Congenital hypothyroidism

NIS

Congenital hypothyroidism

NIS

congenital hypothyroidism

sodium / iodide symporter

congenital hypothyroidism

sodium / iodide symporter

congenital hypothyroidism

NIS

congenital hypothyroidism

NIS

congenital hypothyroidism

NIS

congenital hypothyroidism

NIS

congenital hypothyroidism

sodium / iodide symporter

congenital hypothyroidism

sodium / iodide symporter

congenital hypothyroidism

NIS

congenital hypothyroidism

NIS

congenital hypothyroidism

NIS

congenital hypothyroidism

NIS

Iodide transport defect

sodium / iodide symporter

Iodide transport defect

sodium / iodide symporter

Iodide transport defect

NIS

Iodide transport defect

NIS

Iodide transport defect

NIS

Iodide transport defect

NIS

ITD

sodium / iodide symporter

ITD

sodium / iodide symporter

ITD

NIS

ITD

NIS

ITD

NIS

ITD

NIS

ITD

sodium / iodide symporter

ITD

sodium / iodide symporter

ITD

NIS

ITD

NIS

ITD

NIS

ITD

NIS

ITD

sodium / iodide symporter

ITD

sodium / iodide symporter

ITD

NIS

ITD

NIS

ITD

NIS

ITD

NIS

L - thyroxine

hypothyroidism

L - thyroxine

hypothyroidism

iodide

lacking the five terminal amino acids of exon XI ( 439 - 443 )

iodide

del - ( 439 - 443 )

iodide

lacking the five terminal amino acids of exon XI ( 439 - 443 )

iodide

del - ( 439 - 443 )

iodide

lacking the five terminal amino acids of exon XI ( 439 - 443 )

iodide

del - ( 439 - 443 )

radioiodide

lacking the five terminal amino acids of exon XI ( 439 - 443 )

radioiodide

del - ( 439 - 443 )

I -

lacking the five terminal amino acids of exon XI ( 439 - 443 )

I -

del - ( 439 - 443 )

I -

lacking the five terminal amino acids of exon XI ( 439 - 443 )

I -

del - ( 439 - 443 )

iodide

lacking the five terminal amino acids of exon XI ( 439 - 443 )

iodide

del - ( 439 - 443 )

hypothyroidism

iodide

hypothyroidism

iodide

hypothyroidism

iodide

hypothyroidism

radioiodide

hypothyroidism

I -

hypothyroidism

I -

hypothyroidism

iodide

hypothyroidism

iodide

hypothyroidism

iodide

hypothyroidism

iodide

hypothyroidism

radioiodide

hypothyroidism

I -

hypothyroidism

I -

hypothyroidism

iodide


Input: Pallidal stimulation : an alternative to pallidotomy ? A resurgence of interest in the surgical treatment of Parkinson ' s disease ( PD ) came with the rediscovery of posteroventral pallidotomy by Laitinen in 1985 . Laitinen ' s procedure improved most symptoms in drug - resistant PD , which engendered wide interest in the neurosurgical community . Another lesioning procedure , ventrolateral thalamotomy , has become a powerful alternative to stimulate the nucleus ventralis intermedius , producing high long - term success rates and low morbidity rates . Pallidal stimulation has not met with the same success . According to the literature pallidotomy improves the " on " symptoms of PD , such as dyskinesias , as well as the " off " symptoms , such as rigidity , bradykinesia , and on - off fluctuations . Pallidal stimulation improves bradykinesia and rigidity to a minor extent ; however , its strength seems to be in improving levodopa - induced dyskinesias . Stimulation often produces an improvement in the hyper - or dyskinetic upper limbs , but increases the " freezing " phenomenon in the lower limbs at the same time . Considering the small increase in the patient ' s independence , the high costs of bilateral implants , and the difficulty most patients experience in handling the devices , the question arises as to whether bilateral pallidal stimulation is a real alternative to pallidotomy .

Parkinson ' s disease

PD

PD

PD

dyskinesias

rigidity

bradykinesia

bradykinesia

rigidity

dyskinesias

hyper - or dyskinetic

levodopa

patient

patients

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

hyper - or dyskinetic


Input: Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies . Nijmegen breakage syndrome ( NBS ) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition , in particular to lymphoma and leukemia . Recently , significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation , 657del5 , were found in Russian children with sporadic lymphoid malignancies , and in Polish adults with non - Hodgkin lymphoma ( NHL ) . In addition , the substitution 643C > T ( R215W ) has also been found in excess among children with acute lymphoblastic leukemia ( ALL ) . In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies , we analyzed DNA samples from a large group of Polish pediatric patients . The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL ; no carrier was found among 63 patients with Hodgkin lymphoma ( HL ) . No carriers of the variant R215W were detected in any studied group . The relative frequency of the 657del5 mutation was calculated from a total of 6 , 984 controls matched by place of patient residence , of whom 42 were found to be carriers ( frequency = 0 . 006 ) . In the analyzed population with malignancies , an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population ( OR range 1 . 48 - 1 . 85 , 95 % confidence interval 1 . 18 - 2 . 65 ) . This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL ( p < 0 . 05 ) . Nonetheless , NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence .

643C > T

patients

human

patients

patients

patients

patient

patients

sporadic lymphoid malignancies

Nijmegen breakage syndrome

NBS

autosomal recessive disease

cancer

lymphoma

leukemia

sporadic lymphoid malignancies

non - Hodgkin lymphoma

NHL

acute lymphoblastic leukemia

ALL

sporadic lymphoid malignancies

ALL

NHL

Hodgkin lymphoma

HL

malignancies

ALL

NHL

lymphoid malignancies

cancer

cancer

cancer

cancer

cancer

malignancies

malignancies

malignancies

malignancies

malignancies

acute lymphoblastic leukemia

acute lymphoblastic leukemia

ALL

ALL

ALL

ALL

ALL

ALL

acute lymphoblastic leukemia

643C > T

ALL

643C > T

ALL

643C > T

ALL

643C > T

acute lymphoblastic leukemia

acute lymphoblastic leukemia

acute lymphoblastic leukemia

acute lymphoblastic leukemia

acute lymphoblastic leukemia

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

ALL

cancer

malignancies

cancer

malignancies

cancer

malignancies

cancer

malignancies

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

acute lymphoblastic leukemia

ALL

ALL

ALL

acute lymphoblastic leukemia

ALL

ALL

ALL

acute lymphoblastic leukemia

ALL

ALL

ALL

acute lymphoblastic leukemia

ALL

ALL

ALL

sporadic lymphoid malignancies

lymphoma

sporadic lymphoid malignancies

sporadic lymphoid malignancies

lymphoid malignancies

sporadic lymphoid malignancies

lymphoma

sporadic lymphoid malignancies

sporadic lymphoid malignancies

lymphoid malignancies

sporadic lymphoid malignancies

lymphoma

sporadic lymphoid malignancies

sporadic lymphoid malignancies

lymphoid malignancies

sporadic lymphoid malignancies

lymphoma

sporadic lymphoid malignancies

sporadic lymphoid malignancies

lymphoid malignancies

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

non - Hodgkin lymphoma

NHL

NHL

NHL

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

lymphoma

lymphoma

lymphoma

lymphoma

lymphoma

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

sporadic lymphoid malignancies

lymphoid malignancies

lymphoid malignancies

lymphoid malignancies

lymphoid malignancies

lymphoid malignancies


Input: Segregation of a M404V mutation of the p62 / sequestosome 1 ( p62 / SQSTM1 ) gene with polyostotic Paget ' s disease of bone in an Italian family . Mutations of the p62 / Sequestosome 1 gene ( p62 / SQSTM1 ) account for both sporadic and familial forms of Paget ' s disease of bone ( PDB ) . We originally described a methionine - - > valine substitution at codon 404 ( M404V ) of exon 8 , in the ubiquitin protein - binding domain of p62 / SQSTM1 gene in an Italian PDB patient . The collection of data from the patient ' s pedigree provided evidence for a familial form of PDB . Extension of the genetic analysis to other relatives in this family demonstrated segregation of the M404V mutation with the polyostotic PDB phenotype and provided the identification of six asymptomatic gene carriers . DNA for mutational analysis of the exon 8 coding sequence was obtained from 22 subjects , 4 PDB patients and 18 clinically unaffected members . Of the five clinically ascertained affected members of the family , four possessed the M404V mutation and exhibited the polyostotic form of PDB , except one patient with a single X - ray - assessed skeletal localization and one with a polyostotic disease who had died several years before the DNA analysis . By both reconstitution and mutational analysis of the pedigree , six unaffected subjects were shown to bear the M404V mutation , representing potential asymptomatic gene carriers whose circulating levels of alkaline phosphatase were recently assessed as still within the normal range . Taken together , these results support a genotype - phenotype correlation between the M404V mutation in the p62 / SQSTM1 gene and a polyostotic form of PDB in this family . The high penetrance of the PDB trait in this family together with the study of the asymptomatic gene carriers will allow us to confirm the proposed genotype - phenotype correlation and to evaluate the potential use of mutational analysis of the p62 / SQSTM1 gene in the early detection of relatives at risk for PDB .

methionine - - > valine substitution at codon 404

sequestosome 1

Sequestosome 1

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

polyostotic disease

PDB

PDB

PDB

patient

patient

patients

patient

alkaline phosphatase

polyostotic disease

sequestosome 1

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

Sequestosome 1

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

sequestosome 1

Paget ' s disease of bone

sequestosome 1

Paget ' s disease of bone

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

sequestosome 1

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Sequestosome 1

Paget ' s disease of bone

Sequestosome 1

Paget ' s disease of bone

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Sequestosome 1

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

PDB

polyostotic disease

methionine - - > valine substitution at codon 404

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

polyostotic disease

Paget ' s disease of bone

Paget ' s disease of bone

methionine - - > valine substitution at codon 404

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

methionine - - > valine substitution at codon 404

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

Paget ' s disease of bone

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB

PDB

PDB

methionine - - > valine substitution at codon 404

PDB

PDB

PDB

PDB

PDB


Input: Two distinct mutations at a single BamHI site in phenylketonuria . Classical phenylketonuria is an autosomal recessive disease caused by a deficiency of hepatic phenylalanine hydroxylase ( PAH ) . The abolition of an invariant BamHI site located in the coding sequence of the PAH gene ( exon 7 ) led to the recognition of two new point mutations at codon 272 and 273 ( 272gly - - - - stop and 273ser - - - - phe , respectively ) . Both mutations were detected in north eastern France or Belgium and occurred on the background of RFLP haplotype 7 alleles . The present study supports the view that the clinical heterogeneity in PKU is accounted for by the large variety of mutant genotypes associated with PAH deficiencies . .

phenylketonuria

Classical phenylketonuria

autosomal recessive disease

deficiency of hepatic phenylalanine hydroxylase

PKU

PAH deficiencies

PAH

PAH

272gly - - - - stop

273ser - - - - phe

phenylketonuria

272gly - - - - stop

Classical phenylketonuria

272gly - - - - stop

PKU

272gly - - - - stop

phenylketonuria

273ser - - - - phe

Classical phenylketonuria

273ser - - - - phe

PKU

273ser - - - - phe

272gly - - - - stop

deficiency of hepatic phenylalanine hydroxylase

272gly - - - - stop

PAH deficiencies

273ser - - - - phe

deficiency of hepatic phenylalanine hydroxylase

273ser - - - - phe

PAH deficiencies

PAH

phenylketonuria

PAH

Classical phenylketonuria

PAH

PKU

PAH

phenylketonuria

PAH

Classical phenylketonuria

PAH

PKU

PAH

deficiency of hepatic phenylalanine hydroxylase

PAH

PAH deficiencies

PAH

deficiency of hepatic phenylalanine hydroxylase

PAH

PAH deficiencies


Input: Association of DRD2 polymorphisms and chlorpromazine - induced extrapyramidal syndrome in Chinese schizophrenic patients . AIM : Extrapyramidal syndrome ( EPS ) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor . Recently , many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression . In this study , we evaluate the role DRD2 plays in chlorpromazine - induced EPS in schizophrenic patients . METHODS : We identified seven SNP ( single nucleotide polymorphism ) ( - 141Cins > del , TaqIB , TaqID , Ser311Cys , rs6275 , rs6277 and TaqIA ) in the DRD2 gene in 146 schizophrenic inpatients ( 59 with EPS and 87 without EPS according to the Simpson - Angus Scale ) treated with chlorpromazine after 8 weeks . The alleles of all loci were determined by PCR ( polymerase chain reaction ) . RESULTS : Polymorphisms TaqID , Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study . No statistical significance was found in the allele distribution of - 141Cins > del , TaqIB , rs6275 and TaqIA or in the estimated haplotypes ( constituted by TaqIB , rs6275 and TaqIA ) in linkage disequilibrium between the two groups . CONCLUSION : Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine , at least in Chinese patients with schizophrenia . Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians .

D2 receptor

chlorpromazine

antipsychotic drugs

chlorpromazine

chlorpromazine

chlorpromazine

extrapyramidal syndrome

schizophrenic

Extrapyramidal syndrome

EPS

schizophrenia

EPS

schizophrenic

schizophrenic

EPS

EPS

schizophrenia

EPS

patients

patients

patients

inpatients

patients

- 141Cins > del

- 141Cins > del

schizophrenic

schizophrenia

schizophrenic

schizophrenic

schizophrenia

D2 receptor

schizophrenic

D2 receptor

schizophrenia

D2 receptor

schizophrenic

D2 receptor

schizophrenic

D2 receptor

schizophrenia

schizophrenic

schizophrenia

schizophrenic

schizophrenic

schizophrenia

schizophrenic

schizophrenia

schizophrenic

schizophrenic

schizophrenia

schizophrenic

schizophrenia

schizophrenic

schizophrenic

schizophrenia

schizophrenic

schizophrenia

schizophrenic

schizophrenic

schizophrenia

schizophrenic

schizophrenia

schizophrenic

schizophrenic

schizophrenia

antipsychotic drugs

antipsychotic drugs

D2 receptor

antipsychotic drugs

antipsychotic drugs

antipsychotic drugs

antipsychotic drugs

antipsychotic drugs

extrapyramidal syndrome

extrapyramidal syndrome

D2 receptor

extrapyramidal syndrome

extrapyramidal syndrome

extrapyramidal syndrome

extrapyramidal syndrome

extrapyramidal syndrome

Extrapyramidal syndrome

Extrapyramidal syndrome

D2 receptor

Extrapyramidal syndrome

Extrapyramidal syndrome

Extrapyramidal syndrome

Extrapyramidal syndrome

Extrapyramidal syndrome

EPS

EPS

D2 receptor

EPS

EPS

EPS

EPS

EPS

EPS

EPS

D2 receptor

EPS

EPS

EPS

EPS

EPS

EPS

EPS

D2 receptor

EPS

EPS

EPS

EPS

EPS

EPS

EPS

D2 receptor

EPS

EPS

EPS

EPS

EPS

EPS

EPS

D2 receptor

EPS

EPS

EPS

EPS

EPS

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenia

chlorpromazine

schizophrenia

chlorpromazine

schizophrenia

chlorpromazine

schizophrenia

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenic

chlorpromazine

schizophrenia

chlorpromazine

schizophrenia

chlorpromazine

schizophrenia

chlorpromazine

schizophrenia

chlorpromazine

extrapyramidal syndrome

antipsychotic drugs

Extrapyramidal syndrome

antipsychotic drugs

EPS

antipsychotic drugs

EPS

antipsychotic drugs

EPS

antipsychotic drugs

EPS

antipsychotic drugs

EPS

antipsychotic drugs

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS


Input: A novel IRF6 nonsense mutation ( Y67X ) in a German family with Van der Woude syndrome . Van der Woude syndrome ( VWS ) is the most common type of syndromic orofacial cleft , which accounts for approximately 2 % of all cleft lip and palate cases . It is characterised by variable association of lower lip pits , cleft lip and cleft palate , and hypodontia . VWS arises as the result of mutations in the gene encoding interferon regulatory factor 6 ( IRF6 ) . The disorder is transmitted in an autosomal dominant manner , with high penetrance and variable expressivity . Very recently , mutations of the IRF6 gene in exons 2 - 9 have been found in VWS patients , suggesting that this gene plays an important role in orofacial development . We report a novel mutation of the IRF6 gene in a German family . Five out of the 12 persons affected were able to be investigated . The mutation produced a stop codon within exon 4 of the IRF6 gene . All 5 patients were heterozygous for a base substitution c . 201C > A changing the tyrosine codon at amino acid position 67 into a stop codon ( p . Y67X ) in exon 4 . The premature stop codon was responsible for a truncated protein lacking parts of the DNA - binding domain and the complete Smad - interferon regulatory factor - binding domain probably essential for interactions with the Smad transcription factors .

interferon regulatory factor 6

Smad

interferon regulatory factor

Smad

c . 201C > A

tyrosine codon at amino acid position 67 into a stop

p . Y67X

Van der Woude syndrome

Van der Woude syndrome

VWS

syndromic orofacial cleft

cleft lip and palate

lip pits

cleft lip

cleft palate

hypodontia

VWS

VWS

patients

patients

Smad

Smad

interferon regulatory factor 6

Smad

interferon regulatory factor 6

Smad

Smad

Smad

Smad

Smad

Smad

Smad

Smad

Smad

interferon regulatory factor

Smad

interferon regulatory factor

Smad

Van der Woude syndrome

Van der Woude syndrome

VWS

lip pits

VWS

VWS

interferon regulatory factor 6

Van der Woude syndrome

interferon regulatory factor 6

Van der Woude syndrome

interferon regulatory factor 6

VWS

interferon regulatory factor 6

lip pits

interferon regulatory factor 6

VWS

interferon regulatory factor 6

VWS

Van der Woude syndrome

Van der Woude syndrome

VWS

lip pits

VWS

VWS

Van der Woude syndrome

Van der Woude syndrome

VWS

lip pits

VWS

VWS

Van der Woude syndrome

Van der Woude syndrome

VWS

lip pits

VWS

VWS

Van der Woude syndrome

Van der Woude syndrome

VWS

lip pits

VWS

VWS

interferon regulatory factor

Van der Woude syndrome

interferon regulatory factor

Van der Woude syndrome

interferon regulatory factor

VWS

interferon regulatory factor

lip pits

interferon regulatory factor

VWS

interferon regulatory factor

VWS

Van der Woude syndrome

c . 201C > A

Van der Woude syndrome

c . 201C > A

VWS

c . 201C > A

lip pits

c . 201C > A

VWS

c . 201C > A

VWS

c . 201C > A

Van der Woude syndrome

Van der Woude syndrome

VWS

lip pits

VWS

VWS

tyrosine codon at amino acid position 67 into a stop

Van der Woude syndrome

tyrosine codon at amino acid position 67 into a stop

Van der Woude syndrome

tyrosine codon at amino acid position 67 into a stop

VWS

tyrosine codon at amino acid position 67 into a stop

lip pits

tyrosine codon at amino acid position 67 into a stop

VWS

tyrosine codon at amino acid position 67 into a stop

VWS

p . Y67X

Van der Woude syndrome

p . Y67X

Van der Woude syndrome

p . Y67X

VWS

p . Y67X

lip pits

p . Y67X

VWS

p . Y67X

VWS


Input: Skewed X inactivation in an X linked nystagmus family resulted from a novel , p . R229G , missense mutation in the FRMD7 gene . AIMS : This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus ( NYS ) family . METHODS : Both Xp11 and Xq26 loci were tested by linkage analysis . The 12 exons and intron - exon junctions of the FRMD7 gene were screened by direct sequencing . X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation - sensitive enzyme , followed by PCR of the polymorphic CAG repeat of the androgen receptor gene . RESULTS : The family contained 162 individuals , among whom 28 had NYS . Linkage analysis confirmed the Xq26 locus . A novel missense c . 686C > G mutation , which causes the substitution of a conserved arginine at amino acid position 229 by glycine ( p . R229G ) in exon 8 of the FRMD7 gene , was observed . This change was not documented in 120 control individuals . The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females . Skewed X inactivation was remarkable in the affected females of the family . CONCLUSIONS : A novel p . R229G mutation in the FRMD7 gene causes the NYS phenotype , and skewed X inactivation influences the manifestation of the disease in X linked NYS females .

X linked nystagmus

genetic defect

X linked nystagmus

NYS

NYS

NYS

X linked NYS

p . R229G

CAG repeat

c . 686C > G

arginine at amino acid position 229 by glycine

p . R229G

p . R229G

androgen receptor

X linked nystagmus

X linked nystagmus

X linked nystagmus

X linked nystagmus

X linked nystagmus

X linked nystagmus

X linked nystagmus

X linked nystagmus

NYS

NYS

NYS

NYS

NYS

NYS

NYS

NYS

NYS

NYS

NYS

NYS

X linked NYS

X linked NYS

X linked NYS

X linked NYS

X linked nystagmus

p . R229G

X linked nystagmus

c . 686C > G

X linked nystagmus

arginine at amino acid position 229 by glycine

X linked nystagmus

p . R229G

X linked nystagmus

p . R229G

X linked nystagmus

p . R229G

X linked nystagmus

c . 686C > G

X linked nystagmus

arginine at amino acid position 229 by glycine

X linked nystagmus

p . R229G

X linked nystagmus

p . R229G

NYS

p . R229G

NYS

c . 686C > G

NYS

arginine at amino acid position 229 by glycine

NYS

p . R229G

NYS

p . R229G

NYS

p . R229G

NYS

c . 686C > G

NYS

arginine at amino acid position 229 by glycine

NYS

p . R229G

NYS

p . R229G

NYS

p . R229G

NYS

c . 686C > G

NYS

arginine at amino acid position 229 by glycine

NYS

p . R229G

NYS

p . R229G

X linked NYS

p . R229G

X linked NYS

c . 686C > G

X linked NYS

arginine at amino acid position 229 by glycine

X linked NYS

p . R229G

X linked NYS

p . R229G


Input: Identification of apolipoprotein E Guangzhou ( arginine 150 proline ) , a new variant associated with lipoprotein glomerulopathy . BACKGROUND / AIMS : Lipoprotein glomerulopathy ( LPG ) is a rare disease characterized by thrombus - like substances in markedly dilated glomerular capillaries and elevated plasma levels of apolipoprotein E ( apoE ) . Previous studies have shown that genetic disorders of apoE may contribute to the pathogenesis of LPG , but LPG may not be caused by apoE gene mutations in Chinese patients . This study investigated the association of a new variant of apoE with LPG in a Chinese family . METHODS : The apoE gene in a family with 4 LPG patients was sequenced . The polymerase chain reaction product of coding region of apoE exon 4 was cloned into pMD 18 - T vector and then sequenced . RESULTS : A novel point mutation in exon 4 of the apoE gene was identified in all 4 LPG patients and 1 asymptomatic family member . Sequence analysis confirmed a nucleotide G to C point mutation in exon 4 ( base 308 ) of the apoE gene in all patients and the asymptomatic family member . This missense mutation denotes amino acid substitution of the proline residue for arginine residue at position 150 of apoE . Those patients were all heterozygotes with apoE Guangzhou . One of 2 grandsons was a heterozygous carrier of apoE Guangzhou , although he did not have proteinuria . CONCLUSION : The results of this study suggest that apoE ( arginine 150 proline ) is a novel apoE variant that etiologically related to LPG . This variant ( apoE Guangzhou ) may cause a marked molecular conformational change of the apoE and thus impair its binding ability to lipids .

apolipoprotein E

apolipoprotein E

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

apoE

arginine 150 proline

G to C point mutation in exon 4 ( base 308 )

proline residue for arginine residue at position 150

arginine 150 proline

lipoprotein glomerulopathy

Lipoprotein glomerulopathy

LPG

thrombus

dilated glomerular capillaries

LPG

LPG

LPG

LPG

LPG

proteinuria

LPG

patients

patients

patients

patients

patients

lipids

G to C point mutation in exon 4 ( base 308 )

lipids

apolipoprotein E

lipoprotein glomerulopathy

apolipoprotein E

Lipoprotein glomerulopathy

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

lipoprotein glomerulopathy

apolipoprotein E

Lipoprotein glomerulopathy

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apolipoprotein E

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

lipoprotein glomerulopathy

apoE

Lipoprotein glomerulopathy

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

apoE

LPG

arginine 150 proline

lipids

proline residue for arginine residue at position 150

lipids

arginine 150 proline

lipids

arginine 150 proline

lipoprotein glomerulopathy

arginine 150 proline

Lipoprotein glomerulopathy

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

proline residue for arginine residue at position 150

lipoprotein glomerulopathy

proline residue for arginine residue at position 150

Lipoprotein glomerulopathy

proline residue for arginine residue at position 150

LPG

proline residue for arginine residue at position 150

LPG

proline residue for arginine residue at position 150

LPG

proline residue for arginine residue at position 150

LPG

proline residue for arginine residue at position 150

LPG

proline residue for arginine residue at position 150

LPG

proline residue for arginine residue at position 150

LPG

arginine 150 proline

lipoprotein glomerulopathy

arginine 150 proline

Lipoprotein glomerulopathy

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

arginine 150 proline

LPG

apolipoprotein E

lipids

apolipoprotein E

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids

apoE

lipids


Input: Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography . WHAT IS KNOWN AND OBJECTIVE : CYP2C8 is involved in the cytochrome P450 ( CYP ) epoxygenase pathway . Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids , produced may have a role in hypertension . We aimed to develop a medium through - put method for screening samples of known and new mutations of CYP2C8 using denaturing high performance liquid chromatography ( DHPLC ) . METHODS : DNA samples from 200 subjects ( hypertensive patients and healthy controls ) were screened for SNPs in CYP2C8 using DHPLC . Genotypes and allelic frequencies of CYP2C8 between the healthy controls and patients with hypertension were compared . RESULTS AND DISCUSSIONS : Six variants were detected and two were new ; T deletion at 5063 and substitution of C to T at 33468 in exon 8 . Differences in variant frequencies were detected between the controls and hypertensive patients . The controls have significantly higher prevalence of C35322C compared to the patients . The functional significance of the SNP at 35322 requires further study . Having homozygous C35322C could be a protective factor for hypertension . WHAT IS NEW AND CONCLUSION : Denaturing high performance liquid chromatography is useful for population screening to identify new and existing SNPs . A higher frequency of the C35322T SNP was observed among hypertensive patients than control subjects . This potentially important observation requires confirmation and the clinical significance assessed .

cytochrome P450 ( CYP ) epoxygenase

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive

patients

patients

patients

patients

patients

patients

Arachidonic acid

epoxyeicosatrienenoic acids

hydroxyeicosatetrenoic acids

T deletion at 5063

C to T at 33468

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive

cytochrome P450 ( CYP ) epoxygenase

hypertensive

cytochrome P450 ( CYP ) epoxygenase

hypertension

cytochrome P450 ( CYP ) epoxygenase

hypertensive

cytochrome P450 ( CYP ) epoxygenase

hypertension

cytochrome P450 ( CYP ) epoxygenase

hypertensive

cytochrome P450 ( CYP ) epoxygenase

hypertension

cytochrome P450 ( CYP ) epoxygenase

hypertensive

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive

Arachidonic acid

hypertensive

Arachidonic acid

hypertension

Arachidonic acid

hypertensive

Arachidonic acid

hypertension

Arachidonic acid

hypertensive

Arachidonic acid

hypertension

Arachidonic acid

hypertensive

C to T at 33468

hypertensive

C to T at 33468

hypertension

C to T at 33468

hypertensive

C to T at 33468

hypertension

C to T at 33468

hypertensive

C to T at 33468

hypertension

C to T at 33468

hypertensive

hypertensive

hypertensive

hypertension

hypertension

hypertensive

hypertensive

hypertension

hypertension

hypertensive

hypertensive

hypertension

hypertension

hypertensive

hypertensive

T deletion at 5063

hypertensive

T deletion at 5063

hypertension

T deletion at 5063

hypertensive

T deletion at 5063

hypertension

T deletion at 5063

hypertensive

T deletion at 5063

hypertension

T deletion at 5063

hypertensive

hypertensive

hypertension

hypertensive

hypertension

hypertensive

hypertension

hypertensive


Input: TNFR - associated factor 2 deficiency in B lymphocytes predisposes to chronic lymphocytic leukemia / small lymphocytic lymphoma in mice . We have previously shown that transgenic ( tg ) mice expressing in B lymphocytes both BCL - 2 and a TNFR - associated factor 2 ( TRAF2 ) mutant lacking the really interesting new gene and zinc finger domains ( TRAF2DN ) develop small lymphocytic lymphoma and chronic lymphocytic leukemia with high incidence ( Zapata et al . 2004 . Proc . Nat . Acad . Sci . USA 101 : 16600 - 16605 ) . Further analysis of the expression of TRAF2 and TRAF2DN in purified B cells demonstrated that expression of both endogenous TRAF2 and tg TRAF2DN was negligible in Traf2DN - tg B cells compared with wild - type mice . This was the result of proteasome - dependent degradation , and rendered TRAF2DN B cells as bona fide TRAF2 - deficient B cells . Similar to B cells with targeted Traf2 deletion , Traf2DN - tg mice show expanded marginal zone B cell population and have constitutive p100 NF - kappaB2 processing . Also , TRAF3 , X - linked inhibitor of apoptosis , and Bcl - X ( L ) expression levels were increased , whereas cellular inhibitors of apoptosis 1 and 2 levels were drastically reduced compared with those found in wild - type B cells . Moreover , consistent with previous results , we also show that TRAF2 was required for efficient JNK and ERK activation in response to CD40 engagement . However , TRAF2 was deleterious for BCR - mediated activation of these kinases . In contrast , TRAF2 deficiency had no effect on CD40 - mediated p38 MAPK activation but significantly reduced BCR - mediated p38 activation . Finally , we further confirm that TRAF2 was required for CD40 - mediated proliferation , but its absence relieved B cells of the need for B cell activating factor for survival . Altogether , our results suggest that TRAF2 deficiency cooperates with BCL - 2 in promoting chronic lymphocytic leukemia / small lymphocytic lymphoma in mice , possibly by specifically enforcing marginal zone B cell accumulation , increasing X - linked inhibitor of apoptosis expression , and rendering B cells independent of B cell activating factor for survival .

TNFR - associated factor 2

BCL - 2

TNFR - associated factor 2

proteasome

p100 NF - kappaB2

X - linked inhibitor of apoptosis

Bcl - X ( L )

cellular inhibitors of apoptosis 1 and 2

JNK

ERK

BCR

p38 MAPK

BCR

B cell activating factor

BCL - 2

X - linked inhibitor of apoptosis

B cell activating factor

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

mice

mice

mice

mice

mice

Traf2DN - tg B

Traf2DN - tg

BCL - 2

X - linked inhibitor of apoptosis

BCL - 2

X - linked inhibitor of apoptosis

BCL - 2

X - linked inhibitor of apoptosis

BCL - 2

X - linked inhibitor of apoptosis

BCL - 2

chronic lymphocytic leukemia

BCL - 2

small lymphocytic lymphoma

BCL - 2

small lymphocytic lymphoma

BCL - 2

chronic lymphocytic leukemia

BCL - 2

chronic lymphocytic leukemia

BCL - 2

small lymphocytic lymphoma

BCL - 2

chronic lymphocytic leukemia

BCL - 2

small lymphocytic lymphoma

BCL - 2

small lymphocytic lymphoma

BCL - 2

chronic lymphocytic leukemia

BCL - 2

chronic lymphocytic leukemia

BCL - 2

small lymphocytic lymphoma

BCR

p38 MAPK

BCR

BCR

p38 MAPK

BCR

p38 MAPK

p38 MAPK

p38 MAPK

ERK

ERK

ERK

JNK

JNK

JNK

TNFR - associated factor 2

B cell activating factor

TNFR - associated factor 2

B cell activating factor

TNFR - associated factor 2

B cell activating factor

TNFR - associated factor 2

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

B cell activating factor

TNFR - associated factor 2

BCL - 2

TNFR - associated factor 2

BCL - 2

TNFR - associated factor 2

BCL - 2

TNFR - associated factor 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

BCL - 2

TNFR - associated factor 2

BCR

TNFR - associated factor 2

BCR

TNFR - associated factor 2

BCR

TNFR - associated factor 2

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

BCR

TNFR - associated factor 2

TNFR - associated factor 2

TNFR - associated factor 2

TNFR - associated factor 2

TNFR - associated factor 2

TNFR - associated factor 2

TNFR - associated factor 2

X - linked inhibitor of apoptosis

TNFR - associated factor 2

X - linked inhibitor of apoptosis

TNFR - associated factor 2

X - linked inhibitor of apoptosis

TNFR - associated factor 2

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

X - linked inhibitor of apoptosis

TNFR - associated factor 2

chronic lymphocytic leukemia

TNFR - associated factor 2

small lymphocytic lymphoma

TNFR - associated factor 2

small lymphocytic lymphoma

TNFR - associated factor 2

chronic lymphocytic leukemia

TNFR - associated factor 2

chronic lymphocytic leukemia

TNFR - associated factor 2

small lymphocytic lymphoma

TNFR - associated factor 2

chronic lymphocytic leukemia

TNFR - associated factor 2

small lymphocytic lymphoma

TNFR - associated factor 2

small lymphocytic lymphoma

TNFR - associated factor 2

chronic lymphocytic leukemia

TNFR - associated factor 2

chronic lymphocytic leukemia

TNFR - associated factor 2

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

chronic lymphocytic leukemia

small lymphocytic lymphoma

small lymphocytic lymphoma

chronic lymphocytic leukemia

chronic lymphocytic leukemia

small lymphocytic lymphoma

TNFR - associated factor 2

p38 MAPK

TNFR - associated factor 2

TNFR - associated factor 2

p38 MAPK

TNFR - associated factor 2

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

p38 MAPK

TNFR - associated factor 2

ERK

TNFR - associated factor 2

ERK

ERK

ERK

ERK

ERK

ERK

ERK

ERK

ERK

ERK

ERK

TNFR - associated factor 2

JNK

TNFR - associated factor 2

JNK

JNK

JNK

JNK

JNK

JNK

JNK

JNK

JNK

JNK

JNK


Input: CTR9 / PAF1c regulates molecular lineage identity , histone H3K36 trimethylation and genomic imprinting during preimplantation development . Genome - wide epigenetic reprogramming is required for successful preimplantation development . Inappropriate or deficient chromatin regulation can result in defective lineage specification and loss of genomic imprinting , compromising normal development . Here we report that two members of the RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex ( PAF1 complex ) components , Ctr9 and Rtf1 , are required during mammalian preimplantation development . We demonstrate that Ctr9 - deficient embryos fail to correctly specify lineages at the blastocyst stage . Expression of some lineage specific factors is markedly reduced in Ctr9 knockdown embryos , including Eomes , Elf5 and Sox2 , while others are inappropriately expressed ( Oct4 , Nanog , Gata6 , Fgf4 and Sox17 ) . We also show that several imprinted genes ( Mest , Peg3 , Snrpn and Meg3 ) are aberrantly expressed although allele specific DNA methylation is not altered . We document a loss of histone H3 lysine 36 trimethylation ( H3K36me3 ) in Ctr9 - deficient embryos and confirm that knockdown of either Setd2 or Rtf1 results in similar phenotypes . These findings show that the PAF1 complex is required for mammalian development , likely through regulation of H3K36me3 , and indicate functional conservation of the PAF1 complex from yeast to mammals in vivo .

histone H3K36

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

Eomes

Nanog

Mest

Snrpn

histone H3

PAF1 complex

PAF1 complex

yeast

histone H3K36

histone H3

histone H3K36

histone H3

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

histone H3K36

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

histone H3

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

histone H3K36

PAF1 complex

histone H3

PAF1 complex

PAF1 complex

histone H3K36

histone H3

histone H3K36

histone H3

PAF1 complex

histone H3K36

PAF1 complex

histone H3

PAF1 complex

PAF1 complex

PAF1 complex

histone H3K36

PAF1 complex

histone H3

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

histone H3K36

histone H3

histone H3K36

histone H3

histone H3K36

histone H3

histone H3K36

histone H3

histone H3K36

histone H3

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

Snrpn

Snrpn

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

Snrpn

PAF1 complex

Snrpn

Snrpn

Snrpn

Snrpn

Snrpn

PAF1 complex

Snrpn

PAF1 complex

Snrpn

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

Mest

Mest

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

Mest

PAF1 complex

Mest

Mest

Mest

Mest

Mest

PAF1 complex

Mest

PAF1 complex

Mest

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

Nanog

Nanog

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

Nanog

PAF1 complex

Nanog

Nanog

Nanog

Nanog

Nanog

PAF1 complex

Nanog

PAF1 complex

Nanog

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

Eomes

Eomes

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

Eomes

PAF1 complex

Eomes

Eomes

Eomes

Eomes

Eomes

PAF1 complex

Eomes

PAF1 complex

Eomes

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

RNA polymerase II associated factor , homolog ( Saccharomyces cerevisiae ) complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex

PAF1 complex


Input: Regulation of signal transducer and activator of transcription 3 and apoptotic pathways by betaine attenuates isoproterenol - induced acute myocardial injury in rats . The present study was designed to investigate the cardioprotective effects of betaine on acute myocardial ischemia induced experimentally in rats focusing on regulation of signal transducer and activator of transcription 3 ( STAT3 ) and apoptotic pathways as the potential mechanism underlying the drug effect . Male Sprague Dawley rats were treated with betaine ( 100 , 200 , and 400 mg / kg ) orally for 40 days . Acute myocardial ischemic injury was induced in rats by subcutaneous injection of isoproterenol ( 85 mg / kg ) , for two consecutive days . Serum cardiac marker enzyme , histopathological variables and expression of protein levels were analyzed . Oral administration of betaine ( 200 and 400 mg / kg ) significantly reduced the level of cardiac marker enzyme in the serum and prevented left ventricular remodeling . Western blot analysis showed that isoproterenol - induced phosphorylation of STAT3 was maintained or further enhanced by betaine treatment in myocardium . Furthermore , betaine ( 200 and 400 mg / kg ) treatment increased the ventricular expression of Bcl - 2 and reduced the level of Bax , therefore causing a significant increase in the ratio of Bcl - 2 / Bax . The protective role of betaine on myocardial damage was further confirmed by histopathological examination . In summary , our results showed that betaine pretreatment attenuated isoproterenol - induced acute myocardial ischemia via the regulation of STAT3 and apoptotic pathways .

signal transducer and activator of transcription 3

signal transducer and activator of transcription 3

Bcl - 2

Bax

Bcl - 2

Bax

betaine

isoproterenol

betaine

betaine

isoproterenol

betaine

isoproterenol

betaine

betaine

betaine

betaine

isoproterenol

myocardial injury

myocardial ischemia

myocardial ischemic injury

ventricular remodeling

myocardial damage

myocardial ischemia

rats

rats

rats

rats

myocardial ischemia

isoproterenol

myocardial ischemia

isoproterenol

myocardial ischemia

isoproterenol

myocardial ischemia

isoproterenol

myocardial ischemic injury

isoproterenol

myocardial ischemic injury

isoproterenol

myocardial ischemic injury

isoproterenol

myocardial ischemic injury

isoproterenol

myocardial ischemia

isoproterenol

myocardial ischemia

isoproterenol

myocardial ischemia

isoproterenol

myocardial ischemia

isoproterenol

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial injury

isoproterenol

myocardial damage

isoproterenol

myocardial injury

isoproterenol

myocardial damage

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

betaine

Bcl - 2

myocardial ischemia

signal transducer and activator of transcription 3

myocardial ischemia

signal transducer and activator of transcription 3

myocardial ischemia

myocardial ischemia

myocardial ischemia

myocardial ischemic injury

signal transducer and activator of transcription 3

myocardial ischemic injury

signal transducer and activator of transcription 3

myocardial ischemic injury

myocardial ischemic injury

myocardial ischemic injury

myocardial ischemia

signal transducer and activator of transcription 3

myocardial ischemia

signal transducer and activator of transcription 3

myocardial ischemia

myocardial ischemia

myocardial ischemia

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

isoproterenol

isoproterenol

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

isoproterenol

isoproterenol

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

isoproterenol

isoproterenol

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

signal transducer and activator of transcription 3

isoproterenol

isoproterenol

isoproterenol

myocardial injury

signal transducer and activator of transcription 3

myocardial injury

signal transducer and activator of transcription 3

myocardial injury

myocardial injury

myocardial injury

myocardial damage

signal transducer and activator of transcription 3

myocardial damage

signal transducer and activator of transcription 3

myocardial damage

myocardial damage

myocardial damage

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

signal transducer and activator of transcription 3

betaine

signal transducer and activator of transcription 3

betaine

betaine

betaine

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

Bax

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

ventricular remodeling

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

myocardial ischemia

betaine

myocardial ischemic injury

betaine

myocardial ischemia

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

isoproterenol

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage

betaine

myocardial injury

betaine

myocardial damage


Input: Combination of the histone deacetylase inhibitor depsipeptide and 5 - fluorouracil upregulates major histocompatibility complex class II and p21 genes and activates caspase - 3 / 7 in human colon cancer HCT - 116 cells . Epigenetic anticancer drugs such as histone deacetylase ( HDAC ) inhibitors have been combined with existing anticancer drugs for synergistic or additive effects . In the present study , we found that a very low concentration of depsipeptide , an HDAC inhibitor , potentiated the antitumor activity of 5 - fluorouracil ( 5 - FU ) in a human colon cancer cell model using HCT - 116 , HT29 , and SW48 cells via the inhibition of colony formation ability or cellular viability . Exposure to a combination of 5 - FU ( 1 . 75 uM ) and 1 nM depsipeptide for 24 and 48 h resulted in a 3 - to 4 - fold increase in activated caspase - 3 / 7 , while 5 - FU alone failed to activate caspase - 3 / 7 . Microarray and subsequent gene ontology analyses revealed that compared to 5 - FU or depsipeptide alone , the combination treatment of 5 - FU and depsipeptide upregulated genes related to cell death and the apoptotic process consistent with the inhibition of colony formation and caspase - 3 / 7 activation . These analyses indicated marked upregulation of antigen processing and presentation of peptide or polysaccharide antigen via major histocompatibility complex ( MHC ) class ( GO : 0002504 ) and MHC protein complex ( GO : 0042611 ) . Compared with vehicle controls , the cells treated with the combination of 5 - FU and depsipeptide showed marked induction ( 3 - to 8 . 5 - fold ) of expression of MHC class II genes , but not of MHC class I genes . Furthermore , our global analysis of gene expression , which was focused on genes involved in the molecular regulation of MHC class II genes , showed enhancement of pro - apoptotic PCAF and CIITA after the combination of 5 - FU and depsipeptide . These results may indicate a closer relationship between elevation of MHC class II expression and cellular apoptosis induced by the combination of depsipeptide and 5 - FU . To the best of our knowledge , this is the first study to report that the combination of 5 - FU and depsipeptide induces human colon cancer cell apoptosis in a concerted manner with the induction of MHC class II gene expression .

histone deacetylase

major histocompatibility complex class II

caspase - 3 / 7

histone deacetylase

HDAC

HDAC

caspase - 3 / 7

caspase - 3 / 7

caspase - 3 / 7

major histocompatibility complex ( MHC ) class

MHC protein complex

MHC class II genes

MHC class I genes

MHC class II genes

PCAF

CIITA

MHC class II

MHC class II

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

5 - FU

5 - FU

depsipeptide

5 - FU

5 - FU

depsipeptide

5 - FU

depsipeptide

polysaccharide

5 - FU

depsipeptide

5 - FU

depsipeptide

depsipeptide

5 - FU

5 - FU

depsipeptide

human

human

human

colon cancer

colon cancer

colon cancer

HCT - 116

HCT - 116

polysaccharide

major histocompatibility complex ( MHC ) class

polysaccharide

MHC protein complex

5 - fluorouracil

CIITA

5 - fluorouracil

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - FU

CIITA

5 - fluorouracil

PCAF

5 - fluorouracil

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

5 - FU

PCAF

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

CIITA

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

depsipeptide

PCAF

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

histone deacetylase

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

HDAC

depsipeptide

5 - fluorouracil

colon cancer

5 - fluorouracil

colon cancer

5 - fluorouracil

colon cancer

5 - fluorouracil

colon cancer

5 - fluorouracil

colon cancer

5 - fluorouracil

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

5 - FU

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

depsipeptide

colon cancer

5 - fluorouracil

5 - fluorouracil

5 - FU

5 - FU

5 - FU

5 - FU

5 - FU

5 - FU

5 - FU

5 - FU

5 - FU

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - fluorouracil

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

5 - FU

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

caspase - 3 / 7

depsipeptide

depsipeptide

depsipeptide

depsipeptide

depsipeptide

depsipeptide

depsipeptide

depsipeptide

depsipeptide

depsipeptide

major histocompatibility complex class II

5 - fluorouracil

major histocompatibility complex class II

5 - fluorouracil

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

major histocompatibility complex class II

5 - FU

MHC class II genes

5 - fluorouracil

MHC class II genes

5 - fluorouracil

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - fluorouracil

MHC class II genes

5 - fluorouracil

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II genes

5 - FU

MHC class II

5 - fluorouracil

MHC class II

5 - fluorouracil

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - fluorouracil

MHC class II

5 - fluorouracil

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

MHC class II

5 - FU

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

major histocompatibility complex class II

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II genes

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

MHC class II

depsipeptide

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - fluorouracil

depsipeptide

5 - fluorouracil

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU

depsipeptide

5 - FU


Input: Seven novel and six de novo PHEX gene mutations in patients with hypophosphatemic rickets . Inactivating mutations in phosphate - regulating gene with homologies to endopeptidase on the X chromosome ( PHEX ) have been identified as a cause of X - linked hypophosphatemic rickets ( XLH ; OMIM 307800 ) . In the present study , we enrolled 43 patients from 18 unrelated families clinically diagnosed with hypophosphatemic rickets and 250 healthy controls . For each available individual , all 22 exons with their exon - intron boundaries of the PHEX gene were directly sequenced . The levels of serum fibroblast growth factor 23 ( FGF23 ) were measured as well . Sequencing analysis detected 17 different PHEX gene mutations , and 7 of these were identified as novel : 3 missense mutations , including c . 304G > A ( p . Gly102Arg ) in exon 3 , c . 229T > C ( p . Cys77Arg ) in exon 3 and c . 824T > C ( p . Leu275Pro ) in exon 7 ; 2 deletion mutations , including c . 528delT ( p . Glu177LysfsX44 ) in exon 5 and c . 1234delA ( p . Ser412ValfsX12 ) in exon 11 ; and 2 alternative splicing mutations , including c . 436_436 + 1delAG in intron 4 at splicing donor sites and c . 1483 - 1G > C in intron 13 at splicing acceptor sites . Moreover , 6 mutations were proven to be de novo in 6 sporadic cases and the probands were all females . No mutations were found in the 250 healthy controls . The serum levels of FGF23 varied widely among the patients with XLH , and no significant difference was found when compared with those of the healthy controls . On the whole , the findings of this study provide new insight into the spectrum of PHEX mutations and provide potential evidence of a critical domain in PHEX protein . In addition , the finding of an overlap of the serum FGF23 levels between the patients with XLH and the healthy controls indicates its limited diagnostic value in XLH .

PHEX

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

PHEX

PHEX

fibroblast growth factor 23

PHEX

PHEX

PHEX

patients

patients

patients

patients

hypophosphatemic rickets

X - linked hypophosphatemic rickets

XLH

OMIM 307800

hypophosphatemic rickets

XLH

XLH

XLH

c . 304G > A

p . Gly102Arg

c . 229T > C

p . Cys77Arg

c . 824T > C

p . Leu275Pro

c . 528delT

p . Glu177LysfsX44

c . 1234delA

p . Ser412ValfsX12

c . 436_436 + 1delAG

c . 1483 - 1G > C

X - linked hypophosphatemic rickets

c . 1483 - 1G > C

XLH

c . 1483 - 1G > C

OMIM 307800

c . 1483 - 1G > C

XLH

c . 1483 - 1G > C

XLH

c . 1483 - 1G > C

XLH

c . 1483 - 1G > C

X - linked hypophosphatemic rickets

c . 304G > A

XLH

c . 304G > A

OMIM 307800

c . 304G > A

XLH

c . 304G > A

XLH

c . 304G > A

XLH

c . 304G > A

X - linked hypophosphatemic rickets

c . 229T > C

XLH

c . 229T > C

OMIM 307800

c . 229T > C

XLH

c . 229T > C

XLH

c . 229T > C

XLH

c . 229T > C

X - linked hypophosphatemic rickets

c . 824T > C

XLH

c . 824T > C

OMIM 307800

c . 824T > C

XLH

c . 824T > C

XLH

c . 824T > C

XLH

c . 824T > C

X - linked hypophosphatemic rickets

c . 436_436 + 1delAG

XLH

c . 436_436 + 1delAG

OMIM 307800

c . 436_436 + 1delAG

XLH

c . 436_436 + 1delAG

XLH

c . 436_436 + 1delAG

XLH

c . 436_436 + 1delAG

X - linked hypophosphatemic rickets

p . Ser412ValfsX12

XLH

p . Ser412ValfsX12

OMIM 307800

p . Ser412ValfsX12

XLH

p . Ser412ValfsX12

XLH

p . Ser412ValfsX12

XLH

p . Ser412ValfsX12

X - linked hypophosphatemic rickets

c . 1234delA

XLH

c . 1234delA

OMIM 307800

c . 1234delA

XLH

c . 1234delA

XLH

c . 1234delA

XLH

c . 1234delA

X - linked hypophosphatemic rickets

p . Glu177LysfsX44

XLH

p . Glu177LysfsX44

OMIM 307800

p . Glu177LysfsX44

XLH

p . Glu177LysfsX44

XLH

p . Glu177LysfsX44

XLH

p . Glu177LysfsX44

X - linked hypophosphatemic rickets

c . 528delT

XLH

c . 528delT

OMIM 307800

c . 528delT

XLH

c . 528delT

XLH

c . 528delT

XLH

c . 528delT

X - linked hypophosphatemic rickets

p . Leu275Pro

XLH

p . Leu275Pro

OMIM 307800

p . Leu275Pro

XLH

p . Leu275Pro

XLH

p . Leu275Pro

XLH

p . Leu275Pro

X - linked hypophosphatemic rickets

p . Cys77Arg

XLH

p . Cys77Arg

OMIM 307800

p . Cys77Arg

XLH

p . Cys77Arg

XLH

p . Cys77Arg

XLH

p . Cys77Arg

X - linked hypophosphatemic rickets

p . Gly102Arg

XLH

p . Gly102Arg

OMIM 307800

p . Gly102Arg

XLH

p . Gly102Arg

XLH

p . Gly102Arg

XLH

p . Gly102Arg

hypophosphatemic rickets

c . 1483 - 1G > C

hypophosphatemic rickets

c . 1483 - 1G > C

hypophosphatemic rickets

c . 304G > A

hypophosphatemic rickets

c . 304G > A

hypophosphatemic rickets

c . 229T > C

hypophosphatemic rickets

c . 229T > C

hypophosphatemic rickets

c . 824T > C

hypophosphatemic rickets

c . 824T > C

hypophosphatemic rickets

c . 436_436 + 1delAG

hypophosphatemic rickets

c . 436_436 + 1delAG

hypophosphatemic rickets

p . Ser412ValfsX12

hypophosphatemic rickets

p . Ser412ValfsX12

hypophosphatemic rickets

c . 1234delA

hypophosphatemic rickets

c . 1234delA

hypophosphatemic rickets

p . Glu177LysfsX44

hypophosphatemic rickets

p . Glu177LysfsX44

hypophosphatemic rickets

c . 528delT

hypophosphatemic rickets

c . 528delT

hypophosphatemic rickets

p . Leu275Pro

hypophosphatemic rickets

p . Leu275Pro

hypophosphatemic rickets

p . Cys77Arg

hypophosphatemic rickets

p . Cys77Arg

hypophosphatemic rickets

p . Gly102Arg

hypophosphatemic rickets

p . Gly102Arg

PHEX

X - linked hypophosphatemic rickets

PHEX

XLH

PHEX

OMIM 307800

PHEX

XLH

PHEX

XLH

PHEX

XLH

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

X - linked hypophosphatemic rickets

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

XLH

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

OMIM 307800

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

XLH

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

XLH

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

XLH

PHEX

X - linked hypophosphatemic rickets

PHEX

XLH

PHEX

OMIM 307800

PHEX

XLH

PHEX

XLH

PHEX

XLH

PHEX

X - linked hypophosphatemic rickets

PHEX

XLH

PHEX

OMIM 307800

PHEX

XLH

PHEX

XLH

PHEX

XLH

PHEX

X - linked hypophosphatemic rickets

PHEX

XLH

PHEX

OMIM 307800

PHEX

XLH

PHEX

XLH

PHEX

XLH

PHEX

X - linked hypophosphatemic rickets

PHEX

XLH

PHEX

OMIM 307800

PHEX

XLH

PHEX

XLH

PHEX

XLH

PHEX

X - linked hypophosphatemic rickets

PHEX

XLH

PHEX

OMIM 307800

PHEX

XLH

PHEX

XLH

PHEX

XLH

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

hypophosphatemic rickets

phosphate - regulating gene with homologies to endopeptidase on the X chromosome

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets

PHEX

hypophosphatemic rickets


Input: Localisation of the Becker muscular dystrophy gene on the short arm of the X chromosome by linkage to cloned DNA sequences . A linkage study in 30 Becker muscular dystrophy ( BMD ) kindreds using three cloned DNA sequences from the X chromosome which demonstrate restriction fragment length polymorphisms ( RFLPs ) , suggests that the BMD gene is located on the short arm of the X chromosome , in the p21 region . The genes for Becker and Duchenne dystrophies must therefore be closely linked , if not allelic , and any future DNA probes found to be of practical use in one disorder should be equally applicable to the other . The linkage analysis also provides data on the frequency of recombination along the short arm of the X chromosome , and across the centromeric region . .

Becker muscular dystrophy gene

BMD

Becker muscular dystrophy

BMD

Becker and Duchenne dystrophies

Becker muscular dystrophy gene

Becker muscular dystrophy

Becker muscular dystrophy gene

BMD

Becker muscular dystrophy gene

Becker and Duchenne dystrophies

BMD

Becker muscular dystrophy

BMD

BMD

BMD

Becker and Duchenne dystrophies


Input: X - linked adrenoleukodystrophy ( ALD ) : a novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes . Fragments of the adrenoleukodystrophy ( ALD ) cDNA from a patient with adolescent ALD were amplified by polymerase chain reaction and subcloned . Bidirectional sequencing of the entire coding ALD gene disclosed a cytosine to guanine transversion at nucleotide 1451 in exon five , resulting in substitution of proline 484 by arginine . Five of nine siblings of the patient , comprising two cerebral ALD , one adrenomyeloneuropathy , one Addison only as well as the symptomatic mother ( all accumulating very long chain fatty acids ) carried this mutation , which was not found in the unaffected persons , in five unrelated ALD patients , and in twenty controls . We propose that this missense mutation generated the disease per se as well as the metabolic defect ; the different phenotypes , however , must have originated by means of additional pathogenetic factors . .

X - linked adrenoleukodystrophy

ALD

adrenoleukodystrophy

ALD

ALD

ALD

adrenomyeloneuropathy

Addison

ALD

ALD

ALD

patient

patient

patients

cytosine to guanine transversion at nucleotide 1451

proline 484 by arginine

long chain fatty acids

ALD

Addison

ALD

Addison

X - linked adrenoleukodystrophy

ALD

X - linked adrenoleukodystrophy

ALD

ALD

ALD

ALD

ALD

adrenoleukodystrophy

ALD

adrenoleukodystrophy

ALD

ALD

ALD

ALD

ALD

ALD

ALD

ALD

ALD

ALD

ALD

ALD

ALD

adrenomyeloneuropathy

ALD

adrenomyeloneuropathy

ALD

ALD

ALD

ALD

ALD

cytosine to guanine transversion at nucleotide 1451

X - linked adrenoleukodystrophy

cytosine to guanine transversion at nucleotide 1451

ALD

cytosine to guanine transversion at nucleotide 1451

adrenoleukodystrophy

cytosine to guanine transversion at nucleotide 1451

ALD

cytosine to guanine transversion at nucleotide 1451

ALD

cytosine to guanine transversion at nucleotide 1451

ALD

cytosine to guanine transversion at nucleotide 1451

adrenomyeloneuropathy

cytosine to guanine transversion at nucleotide 1451

ALD

proline 484 by arginine

X - linked adrenoleukodystrophy

proline 484 by arginine

ALD

proline 484 by arginine

adrenoleukodystrophy

proline 484 by arginine

ALD

proline 484 by arginine

ALD

proline 484 by arginine

ALD

proline 484 by arginine

adrenomyeloneuropathy

proline 484 by arginine

ALD

cytosine to guanine transversion at nucleotide 1451

Addison

proline 484 by arginine

Addison


Input: Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two - colour fluorescence analysis . The ability to scan a large gene rapidly and accurately for all possible heterozygous mutations in large numbers of patient samples will be critical for the future of medicine . We have designed high - density arrays consisting of over 96 , 600 oligonucleotides 20 - nucleotides ( nt ) in length to screen for a wide range of heterozygous mutations in the 3 . 45 - kilobases ( kb ) exon 11 of the hereditary breast and ovarian cancer gene BRCA1 . Reference and test samples were co - hybridized to these arrays and differences in hybridization patterns quantitated by two - colour analysis . Fourteen of fifteen patient samples with known mutations were accurately diagnosed , and no false positive mutations were identified in 20 control samples . Eight single nucleotide polymorphisms were also readily detected . DNA chip - based assays may provide a valuable new technology for high - throughput cost - efficient detection of genetic alterations .

breast and ovarian cancer gene

patient

patient


Input: Single nucleotide polymorphisms of the HNF4alpha gene are associated with the conversion to type 2 diabetes mellitus : the STOP - NIDDM trial . Hepatocyte nuclear factor 4alpha ( HNF4alpha ) is a transcription factor , which is necessary for normal function of human liver and pancreatic islets . We investigated whether single nucleotide polymorphisms ( SNPs ) of HNF4A , encoding HNF4alpha , influenced the conversion from impaired glucose tolerance ( IGT ) to type 2 diabetes mellitus in subjects of the STOP - NIDDM trial . This trial aimed at evaluating the effect of acarbose compared to placebo in the prevention of type 2 diabetes mellitus . Eight SNPs covering the intragenic and alternate P2 promoter regions of HNF4A were genotyped in study samples using the TaqMan Allelic Discrimination Assays . Three SNPs in the P2 promoter region ( rs4810424 , rs1884614 , and rs2144908 ) were in almost complete association ( D ' > 0 . 97 , r ( 2 ) > 0 . 95 ) and , therefore , only rs4810424 was included in further analyses . Female carriers of the less frequent C allele of rs4810424 had a 1 . 7 - fold elevated risk [ 95 % confidence interval ( CI ) 1 . 09 - 2 . 66 ; P = 0 . 020 ] for the conversion to diabetes compared to women with the common genotype after the adjustment for age , treatment group ( placebo or acarbose ) , smoking , weight at baseline , and weight change . No association was found in men . Haplotype analysis based on three SNPs ( rs4810424 , rs2071197 , and rs3818247 ) representing the linkage disequilibrium blocks in our study population indicated that the conversion to type 2 diabetes mellitus was dependent on the number of risk alleles in different haplotypes in women . Our results suggest that SNPs of HNF4A and their haplotypes predispose to type 2 diabetes mellitus in female subjects of the STOP - NIDDM study population .

Hepatocyte nuclear factor 4alpha

type 2 diabetes mellitus

impaired glucose tolerance

IGT

type 2 diabetes mellitus

type 2 diabetes mellitus

diabetes

type 2 diabetes mellitus

type 2 diabetes mellitus

human

women

men

women

acarbose

acarbose

diabetes

diabetes

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

Hepatocyte nuclear factor 4alpha

type 2 diabetes mellitus

Hepatocyte nuclear factor 4alpha

type 2 diabetes mellitus

Hepatocyte nuclear factor 4alpha

type 2 diabetes mellitus

Hepatocyte nuclear factor 4alpha

type 2 diabetes mellitus

Hepatocyte nuclear factor 4alpha

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

diabetes

diabetes

diabetes

diabetes

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

type 2 diabetes mellitus

acarbose

impaired glucose tolerance

acarbose

IGT

acarbose

impaired glucose tolerance

acarbose

IGT

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus

acarbose

type 2 diabetes mellitus