ferrazzipietro/ncbi_disease · Datasets at Hugging Face

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Identification of APC2 , a homologue of the adenomatous polyposis coli tumour suppressor .	[ { "offsets": [ 44, 77 ], "text": "adenomatous polyposis coli tumour", "type": "Disease" } ]
The adenomatous polyposis coli ( APC ) tumour - suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3beta ( GSK - 3beta ) , axin / conductin and betacatenin .	[ { "offsets": [ 4, 45 ], "text": "adenomatous polyposis coli ( APC ) tumour", "type": "Disease" } ]
Complex formation induces the rapid degradation of betacatenin .	[]
In colon carcinoma cells , loss of APC leads to the accumulation of betacatenin in the nucleus , where it binds to and activates the Tcf - 4 transcription factor ( reviewed in [ 1 ] [ 2 ] ) .	[ { "offsets": [ 3, 18 ], "text": "colon carcinoma", "type": "Disease" } ]
Here , we report the identification and genomic structure of APC homologues .	[]
Mammalian APC2 , which closely resembles APC in overall domain structure , was functionally analyzed and shown to contain two SAMP domains , both of which are required for binding to conductin .	[]
Like APC , APC2 regulates the formation of active betacatenin - Tcf complexes , as demonstrated using transient transcriptional activation assays in APC - / - colon carcinoma cells .	[ { "offsets": [ 159, 174 ], "text": "colon carcinoma", "type": "Disease" } ]
Human APC2 maps to chromosome 19p13 .	[]
3 .	[]
APC and APC2 may therefore have comparable functions in development and cancer .	[ { "offsets": [ 72, 78 ], "text": "cancer", "type": "Disease" } ]
A common MSH2 mutation in English and North American HNPCC families : origin , phenotypic expression , and sex specific differences in colorectal cancer .	[ { "offsets": [ 53, 58 ], "text": "HNPCC", "type": "Disease" }, { "offsets": [ 135, 152 ], "text": "colorectal cancer", "type": "Disease" } ]
The frequency , origin , and phenotypic expression of a germline MSH2 gene mutation previously identified in seven kindreds with hereditary non - polyposis cancer syndrome ( HNPCC ) was investigated .	[ { "offsets": [ 129, 171 ], "text": "hereditary non - polyposis cancer syndrome", "type": "Disease" }, { "offsets": [ 174, 179 ], "text": "HNPCC", "type": "Disease" } ]
The mutation ( A - - > T at nt943 + 3 ) disrupts the 3 splice site of exon 5 leading to the deletion of this exon from MSH2 mRNA and represents the only frequent MSH2 mutation so far reported .	[]
Although this mutation was initially detected in four of 33 colorectal cancer families analysed from eastern England , more extensive analysis has reduced the frequency to four of 52 ( 8 % ) English HNPCC kindreds analysed .	[ { "offsets": [ 60, 77 ], "text": "colorectal cancer", "type": "Disease" }, { "offsets": [ 199, 204 ], "text": "HNPCC", "type": "Disease" } ]
In contrast , the MSH2 mutation was identified in 10 of 20 ( 50 % ) separately identified colorectal families from Newfoundland .	[ { "offsets": [ 90, 100 ], "text": "colorectal", "type": "Disease" } ]
To investigate the origin of this mutation in colorectal cancer families from England ( n = 4 ) , Newfoundland ( n = 10 ) , and the United States ( n = 3 ) , haplotype analysis using microsatellite markers linked to MSH2 was performed .	[ { "offsets": [ 46, 63 ], "text": "colorectal cancer", "type": "Disease" } ]
Within the English and US families there was little evidence for a recent common origin of the MSH2 splice site mutation in most families .	[]
In contrast , a common haplotype was identified at the two flanking markers ( CA5 and D2S288 ) in eight of the Newfoundland families .	[]
These findings suggested a founder effect within Newfoundland similar to that reported by others for two MLH1 mutations in Finnish HNPCC families .	[ { "offsets": [ 131, 136 ], "text": "HNPCC", "type": "Disease" } ]
We calculated age related risks of all , colorectal , endometrial , and ovarian cancers in nt943 + 3 A - - > T MSH2 mutation carriers ( n = 76 ) for all patients and for men and women separately .	[ { "offsets": [ 41, 87 ], "text": "colorectal , endometrial , and ovarian cancers", "type": "Disease" } ]
For both sexes combined , the penetrances at age 60 years for all cancers and for colorectal cancer were 0 .	[ { "offsets": [ 66, 73 ], "text": "cancers", "type": "Disease" }, { "offsets": [ 82, 99 ], "text": "colorectal cancer", "type": "Disease" } ]
86 and 0 .	[]
57 , respectively .	[]
The risk of colorectal cancer was significantly higher ( p < 0 . 01 ) in males than females ( 0 . 63 v 0 . 30 and 0 . 84 v 0 . 44 at ages 50 and 60 years , respectively ) .	[ { "offsets": [ 12, 29 ], "text": "colorectal cancer", "type": "Disease" } ]
For females there was a high risk of endometrial cancer ( 0 . 5 at age 60 years ) and premenopausal ovarian cancer ( 0 . 2 at 50 years ) .	[ { "offsets": [ 37, 55 ], "text": "endometrial cancer", "type": "Disease" }, { "offsets": [ 86, 114 ], "text": "premenopausal ovarian cancer", "type": "Disease" } ]
These intersex differences in colorectal cancer risks have implications for screening programmes and for attempts to identify colorectal cancer susceptibility modifiers .	[ { "offsets": [ 30, 47 ], "text": "colorectal cancer", "type": "Disease" }, { "offsets": [ 126, 143 ], "text": "colorectal cancer", "type": "Disease" } ]
Age of onset in Huntington disease : sex specific influence of apolipoprotein E genotype and normal CAG repeat length .	[ { "offsets": [ 16, 34 ], "text": "Huntington disease", "type": "Disease" } ]
Age of onset ( AO ) of Huntington disease ( HD ) is known to be correlated with the length of an expanded CAG repeat in the HD gene .	[ { "offsets": [ 23, 41 ], "text": "Huntington disease", "type": "Disease" }, { "offsets": [ 44, 46 ], "text": "HD", "type": "Disease" }, { "offsets": [ 124, 126 ], "text": "HD", "type": "Disease" } ]
Apolipoprotein E ( APOE ) genotype , in turn , is known to influence AO in Alzheimer disease , rendering the APOE gene a likely candidate to affect AO in other neurological diseases too .	[ { "offsets": [ 75, 92 ], "text": "Alzheimer disease", "type": "Disease" }, { "offsets": [ 160, 181 ], "text": "neurological diseases", "type": "Disease" } ]
We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length .	[ { "offsets": [ 74, 76 ], "text": "HD", "type": "Disease" }, { "offsets": [ 90, 92 ], "text": "HD", "type": "Disease" } ]
Genotyping for APOE was performed blind to clinical information .	[]
In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients , we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females .	[ { "offsets": [ 99, 101 ], "text": "HD", "type": "Disease" } ]
Such a sex difference in AO was not apparent for any of the other APOE genotypes .	[]
Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO .	[ { "offsets": [ 66, 83 ], "text": "neurodegeneration", "type": "Disease" }, { "offsets": [ 87, 89 ], "text": "HD", "type": "Disease" } ]
Familial deficiency of the seventh component of complement associated with recurrent bacteremic infections due to Neisseria .	[ { "offsets": [ 0, 58 ], "text": "Familial deficiency of the seventh component of complement", "type": "Disease" }, { "offsets": [ 85, 123 ], "text": "bacteremic infections due to Neisseria", "type": "Disease" } ]
The serum of a 29 - year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity .	[ { "offsets": [ 60, 93 ], "text": "disseminated gonococcal infection", "type": "Disease" }, { "offsets": [ 111, 135 ], "text": "meningococcal meningitis", "type": "Disease" }, { "offsets": [ 140, 149 ], "text": "arthritis", "type": "Disease" } ]
The seventh component of complement ( C7 ) was not detected by functional or immunochemical assays , whereas other components were normal by hemolytic and immunochemical assessment .	[]
Her fresh serum lacked complement - mediated bactericidal activity against Neisseria gonorrhoeae , but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity .	[]
The absence of functional C7 activity could not be accounted for on the basis of an inhibitor .	[ { "offsets": [ 4, 28 ], "text": "absence of functional C7", "type": "Disease" } ]
Opsonization and generation of chemotactic activity functioned normally .	[]
Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this siblings clinically well eight - year - old son .	[ { "offsets": [ 0, 22 ], "text": "Complete absence of C7", "type": "Disease" }, { "offsets": [ 86, 110 ], "text": "meningococcal meningitis", "type": "Disease" }, { "offsets": [ 115, 124 ], "text": "arthritis", "type": "Disease" } ]
HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci .	[ { "offsets": [ 104, 117 ], "text": "C7 deficiency", "type": "Disease" } ]
This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections .	[ { "offsets": [ 42, 55 ], "text": "C7 deficiency", "type": "Disease" }, { "offsets": [ 178, 209 ], "text": "bacteremic neisseria infections", "type": "Disease" } ]
Increased incidence of cancer in patients with cartilage - hair hypoplasia .	[ { "offsets": [ 23, 29 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 47, 74 ], "text": "cartilage - hair hypoplasia", "type": "Disease" } ]
OBJECTIVE Previous reports have suggested an increased risk of cancer among patients with cartilage - hair hypoplasia ( CHH ) .	[ { "offsets": [ 63, 69 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 90, 117 ], "text": "cartilage - hair hypoplasia", "type": "Disease" }, { "offsets": [ 120, 123 ], "text": "CHH", "type": "Disease" } ]
This study was carried out to further evaluate this risk among patients with CHH and their first - degree relatives .	[ { "offsets": [ 77, 80 ], "text": "CHH", "type": "Disease" } ]
STUDY DESIGN One hundred twenty - two patients with CHH were identified through 2 countrywide epidemiologic surveys in 1974 and in 1986 .	[ { "offsets": [ 52, 55 ], "text": "CHH", "type": "Disease" } ]
Their parents and nonaffected siblings were identified through the Population Register Center .	[]
This cohort underwent follow - up for cancer incidence through the Finnish Cancer Registry to the end of 1995 .	[ { "offsets": [ 38, 44 ], "text": "cancer", "type": "Disease" } ]
RESULTS A statistically significant excess risk of cancer was seen among the patients with CHH ( standardized incidence ratio 6 . 9 , 95 % confidence interval 2 . 3 to 16 ) , which was mainly attributable to non - Hodgkins lymphoma ( standardized incidence ratio 90 , 95 % confidence interval 18 to 264 ) .	[ { "offsets": [ 51, 57 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 91, 94 ], "text": "CHH", "type": "Disease" }, { "offsets": [ 208, 231 ], "text": "non - Hodgkins lymphoma", "type": "Disease" } ]
In addition , a significant excess risk of basal cell carcinoma was seen ( standardized incidence ratio 35 , 95 % confidence interval 7 . 2 to 102 ) .	[ { "offsets": [ 43, 63 ], "text": "basal cell carcinoma", "type": "Disease" } ]
The cancer incidence among the siblings or the parents did not differ from the average cancer incidence in the Finnish population .	[ { "offsets": [ 4, 10 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 87, 93 ], "text": "cancer", "type": "Disease" } ]
CONCLUSIONS This study confirms an increased risk of cancer , especially non - Hodgkins lymphoma , probably attributable to defective immunity , among patients with CHH .	[ { "offsets": [ 53, 59 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 73, 96 ], "text": "non - Hodgkins lymphoma", "type": "Disease" }, { "offsets": [ 165, 168 ], "text": "CHH", "type": "Disease" } ]
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency .	[ { "offsets": [ 40, 82 ], "text": "dihydropyrimidine dehydrogenase deficiency", "type": "Disease" } ]
Dihydropyrimidine dehydrogenase ( DPD ) deficiency is an autosomal recessive disease characterised by thymine - uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype .	[ { "offsets": [ 0, 50 ], "text": "Dihydropyrimidine dehydrogenase ( DPD ) deficiency", "type": "Disease" }, { "offsets": [ 57, 84 ], "text": "autosomal recessive disease", "type": "Disease" } ]
In order to understand the genetic and phenotypic basis for DPD deficiency , we have reviewed 17 families presenting 22 patients with complete deficiency of DPD .	[ { "offsets": [ 60, 74 ], "text": "DPD deficiency", "type": "Disease" }, { "offsets": [ 143, 160 ], "text": "deficiency of DPD", "type": "Disease" } ]
In this group of patients , 7 different mutations have been identified , including 2 deletions [ 295 - 298delTCAT , 1897delC ] , 1 splice - site mutation [ IVS14 + 1G > A ) ] and 4 missense mutations ( 85T > C , 703C > T , 2658G > A , 2983G > T ) .	[]
Analysis of the prevalence of the various mutations among DPD patients has shown that the G - - > A point mutation in the invariant splice donor site is by far the most common ( 52 % ) , whereas the other six mutations are less frequently observed .	[ { "offsets": [ 58, 61 ], "text": "DPD", "type": "Disease" } ]
A large phenotypic variability has been observed , with convulsive disorders , motor retardation and mental retardation being the most abundant manifestations .	[ { "offsets": [ 56, 76 ], "text": "convulsive disorders", "type": "Disease" }, { "offsets": [ 79, 96 ], "text": "motor retardation", "type": "Disease" }, { "offsets": [ 101, 119 ], "text": "mental retardation", "type": "Disease" } ]
A clear correlation between the genotype and phenotype has not been established .	[]
An altered beta - alanine , uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency .	[ { "offsets": [ 86, 108 ], "text": "clinical abnormalities", "type": "Disease" }, { "offsets": [ 138, 152 ], "text": "DPD deficiency", "type": "Disease" } ]
Fibroblast growth factor homologous factor 2 ( FHF2 ) : gene structure , expression and mapping to the Borjeson - Forssman - Lehmann syndrome region in Xq26 delineated by a duplication breakpoint in a BFLS - like patient .	[ { "offsets": [ 103, 141 ], "text": "Borjeson - Forssman - Lehmann syndrome", "type": "Disease" }, { "offsets": [ 201, 205 ], "text": "BFLS", "type": "Disease" } ]
Borjeson - Forssman - Lehmann syndrome ( BFLS ) is a syndromal X - linked mental retardation , which maps by linkage to the q26 region of the human X chromosome .	[ { "offsets": [ 0, 38 ], "text": "Borjeson - Forssman - Lehmann syndrome", "type": "Disease" }, { "offsets": [ 41, 45 ], "text": "BFLS", "type": "Disease" }, { "offsets": [ 63, 92 ], "text": "X - linked mental retardation", "type": "Disease" } ]
We have identified a male patient with BFLS - like features and a duplication , 46 , Y , dup ( X ) ( q26q28 ) , inherited from his phenotypically normal mother .	[ { "offsets": [ 39, 43 ], "text": "BFLS", "type": "Disease" } ]
Fluorescence in situ hybridisation using yeast artificial chromosome clones from Xq26 localised the duplication breakpoint to an approximately 400 - kb interval in the Xq26 .	[]
3 region between DXS155 and DXS294 / DXS730 .	[]
Database searches and analysis of available genomic DNA sequence from the region revealed the presence of the fibroblast growth factor homologous factor gene , FHF2 , within the duplication breakpoint interval .	[]
The gene structure of FHF2 was determined and two new exons were identified , including a new 5 end exon , 1B .	[]
FHF2 is a large gene extending over approximately 200 kb in Xq26 .	[]
3 and is composed of at least seven exons .	[]
It shows tissue - specific alternative splicing and alternative transcription starts .	[]
Northern blot hybridisation showed highest expression in brain and skeletal muscle .	[]
The FHF2 gene localisation and tissue - specific expression pattern suggest it to be a candidate gene for familial cases of the BFLS syndrome and other syndromal and non - specific forms of X - linked mental retardation mapping to the region .	[ { "offsets": [ 128, 141 ], "text": "BFLS syndrome", "type": "Disease" }, { "offsets": [ 190, 219 ], "text": "X - linked mental retardation", "type": "Disease" } ]
Germline E - cadherin gene ( CDH1 ) mutations predispose to familial gastric cancer and colorectal cancer .	[ { "offsets": [ 60, 83 ], "text": "familial gastric cancer", "type": "Disease" }, { "offsets": [ 88, 105 ], "text": "colorectal cancer", "type": "Disease" } ]
Inherited mutations in the E - cadherin gene ( CDH1 ) were described recently in three Maori kindreds with familial gastric cancer .	[ { "offsets": [ 107, 130 ], "text": "familial gastric cancer", "type": "Disease" } ]
Familial gastric cancer is genetically heterogeneous and it is not clear what proportion of gastric cancer susceptibility in non - Maori populations is due to germline CDH1 mutations .	[ { "offsets": [ 0, 23 ], "text": "Familial gastric cancer", "type": "Disease" }, { "offsets": [ 92, 106 ], "text": "gastric cancer", "type": "Disease" } ]
Therefore , we screened eight familial gastric cancer kindreds of British and Irish origin for germline CDH1 mutations , by SSCP analysis of all 16 exons and flanking sequences .	[ { "offsets": [ 30, 53 ], "text": "familial gastric cancer", "type": "Disease" } ]
Each family contained ( i ) two cases of gastric cancer in first degree relatives with one affected before age 50 years ; or ( ii ) three or more cases of gastric cancer .	[ { "offsets": [ 41, 55 ], "text": "gastric cancer", "type": "Disease" }, { "offsets": [ 155, 169 ], "text": "gastric cancer", "type": "Disease" } ]
Novel germline CDH1 mutations ( a nonsense and a splice site ) were detected in two families ( 25 % ) .	[]
Both mutations were predicted to truncate the E - cadherin protein in the signal peptide domain .	[]
In one family there was evidence of non - penetrance and susceptibility to both gastric and colorectal cancer ; thus , in addition to six cases of gastric cancer , a CDH1 mutation carrier developed colorectal cancer at age 30 years .	[ { "offsets": [ 80, 109 ], "text": "gastric and colorectal cancer", "type": "Disease" }, { "offsets": [ 147, 161 ], "text": "gastric cancer", "type": "Disease" }, { "offsets": [ 198, 215 ], "text": "colorectal cancer", "type": "Disease" } ]
We have confirmed that germline mutations in the CDH1 gene cause familial gastric cancer in non - Maori populations .	[ { "offsets": [ 65, 88 ], "text": "familial gastric cancer", "type": "Disease" } ]
However , only a minority of familial gastric cancers can be accounted for by CDH1 mutations .	[ { "offsets": [ 38, 53 ], "text": "gastric cancers", "type": "Disease" } ]
Loss of E - cadherin function has been implicated in the pathogenesis of sporadic colorectal and other cancers , and our findings provide evidence that germline CDH1 mutations predispose to early onset colorectal cancer .	[ { "offsets": [ 82, 110 ], "text": "colorectal and other cancers", "type": "Disease" }, { "offsets": [ 202, 219 ], "text": "colorectal cancer", "type": "Disease" } ]
Thus , CDH1 should be investigated as a cause of inherited susceptibility to both gastric and colorectal cancers .	[ { "offsets": [ 82, 112 ], "text": "gastric and colorectal cancers", "type": "Disease" } ]
A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys - Drash syndrome .	[ { "offsets": [ 69, 93 ], "text": "urogenital abnormalities", "type": "Disease" }, { "offsets": [ 97, 119 ], "text": "Denys - Drash syndrome", "type": "Disease" } ]
The Wilms tumor - suppressor gene , WT1 , plays a key role in urogenital development , and WT1 dysfunction is implicated in both neoplastic ( Wilms tumor , mesothelioma , leukemias , and breast cancer ) and nonneoplastic ( glomerulosclerosis ) disease .	[ { "offsets": [ 4, 15 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 91, 106 ], "text": "WT1 dysfunction", "type": "Disease" }, { "offsets": [ 129, 139 ], "text": "neoplastic", "type": "Disease" }, { "offsets": [ 142, 153 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 156, 168 ], "text": "mesothelioma", "type": "Disease" }, { "offsets": [ 171, 180 ], "text": "leukemias", "type": "Disease" }, { "offsets": [ 187, 200 ], "text": "breast cancer", "type": "Disease" }, { "offsets": [ 207, 220 ], "text": "nonneoplastic", "type": "Disease" }, { "offsets": [ 223, 241 ], "text": "glomerulosclerosis", "type": "Disease" } ]
The analysis of diseases linked specifically with WT1 mutations , such as Denys - Drash syndrome ( DDS ) , can provide valuable insight concerning the role of WT1 in development and disease .	[ { "offsets": [ 74, 96 ], "text": "Denys - Drash syndrome", "type": "Disease" }, { "offsets": [ 99, 102 ], "text": "DDS", "type": "Disease" } ]
DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis , XY pseudohermaphroditism , and / or Wilms tumor ( WT ) .	[ { "offsets": [ 0, 3 ], "text": "DDS", "type": "Disease" }, { "offsets": [ 51, 62 ], "text": "nephropathy", "type": "Disease" }, { "offsets": [ 73, 92 ], "text": "mesangial sclerosis", "type": "Disease" }, { "offsets": [ 98, 119 ], "text": "pseudohermaphroditism", "type": "Disease" }, { "offsets": [ 131, 142 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 145, 147 ], "text": "WT", "type": "Disease" } ]
DDS patients are constitutionally heterozygous for exonic point mutations in WT1 , which include mutations predicted to truncate the protein within the C - terminal zinc finger ( ZF ) region .	[ { "offsets": [ 0, 3 ], "text": "DDS", "type": "Disease" } ]
We report that heterozygosity for a targeted murine Wt1 allele , Wt1 ( tmT396 ) , which truncates ZF3 at codon 396 , induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice .	[ { "offsets": [ 125, 144 ], "text": "mesangial sclerosis", "type": "Disease" }, { "offsets": [ 163, 166 ], "text": "DDS", "type": "Disease" } ]
Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event , implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice .	[ { "offsets": [ 0, 20 ], "text": "Male genital defects", "type": "Disease" }, { "offsets": [ 70, 81 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 197, 212 ], "text": "Wt1 dysfunction", "type": "Disease" }, { "offsets": [ 217, 236 ], "text": "Wilms tumorigenesis", "type": "Disease" } ]
However , the mutant WT1 ( tmT396 ) protein accounted for only 5 % of WT1 in both heterozygous embryonic stem cells and the WT .	[ { "offsets": [ 124, 126 ], "text": "WT", "type": "Disease" } ]
This has implications regarding the mechanism by which the mutant allele exerts its effect .	[]
Mechanism of increased iron absorption in murine model of hereditary hemochromatosis : increased duodenal expression of the iron transporter DMT1 .	[ { "offsets": [ 58, 84 ], "text": "hereditary hemochromatosis", "type": "Disease" } ]
Hereditary hemochromatosis ( HH ) is a common autosomal recessive disorder characterized by tissue iron deposition secondary to excessive dietary iron absorption .	[ { "offsets": [ 0, 26 ], "text": "Hereditary hemochromatosis", "type": "Disease" }, { "offsets": [ 29, 31 ], "text": "HH", "type": "Disease" }, { "offsets": [ 46, 74 ], "text": "autosomal recessive disorder", "type": "Disease" } ]
We recently reported that HFE , the protein defective in HH , was physically associated with the transferrin receptor ( TfR ) in duodenal crypt cells and proposed that mutations in HFE attenuate the uptake of transferrin - bound iron from plasma by duodenal crypt cells , leading to up - regulation of transporters for dietary iron .	[ { "offsets": [ 57, 59 ], "text": "HH", "type": "Disease" } ]
Here , we tested the hypothesis that HFE - / - mice have increased duodenal expression of the divalent metal transporter ( DMT1 ) .	[]
By 4 weeks of age , the HFE - / - mice demonstrated iron loading when compared with HFE + / + littermates , with elevated transferrin saturations ( 68 . 4 % vs . 49 . 8 % ) and elevated liver iron concentrations ( 985 micrograms vs . 381 micrograms ) .	[]
By using Northern blot analyses , we quantitated duodenal expression of both classes of DMT1 transcripts one containing an iron responsive element ( IRE ) , called DMT1 ( IRE ) , and one containing no IRE , called DMT1 ( non - IRE ) .	[]

Identification of APC2 , a homologue of the adenomatous polyposis coli tumour suppressor .

[ { "offsets": [ 44, 77 ], "text": "adenomatous polyposis coli tumour", "type": "Disease" } ]

The adenomatous polyposis coli ( APC ) tumour - suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3beta ( GSK - 3beta ) , axin / conductin and betacatenin .

[ { "offsets": [ 4, 45 ], "text": "adenomatous polyposis coli ( APC ) tumour", "type": "Disease" } ]

Complex formation induces the rapid degradation of betacatenin .

[]

In colon carcinoma cells , loss of APC leads to the accumulation of betacatenin in the nucleus , where it binds to and activates the Tcf - 4 transcription factor ( reviewed in [ 1 ] [ 2 ] ) .

[ { "offsets": [ 3, 18 ], "text": "colon carcinoma", "type": "Disease" } ]

Here , we report the identification and genomic structure of APC homologues .

[]

Mammalian APC2 , which closely resembles APC in overall domain structure , was functionally analyzed and shown to contain two SAMP domains , both of which are required for binding to conductin .

[]

Like APC , APC2 regulates the formation of active betacatenin - Tcf complexes , as demonstrated using transient transcriptional activation assays in APC - / - colon carcinoma cells .

[ { "offsets": [ 159, 174 ], "text": "colon carcinoma", "type": "Disease" } ]

Human APC2 maps to chromosome 19p13 .

[]

3 .

[]

APC and APC2 may therefore have comparable functions in development and cancer .

[ { "offsets": [ 72, 78 ], "text": "cancer", "type": "Disease" } ]

A common MSH2 mutation in English and North American HNPCC families : origin , phenotypic expression , and sex specific differences in colorectal cancer .

[ { "offsets": [ 53, 58 ], "text": "HNPCC", "type": "Disease" }, { "offsets": [ 135, 152 ], "text": "colorectal cancer", "type": "Disease" } ]

The frequency , origin , and phenotypic expression of a germline MSH2 gene mutation previously identified in seven kindreds with hereditary non - polyposis cancer syndrome ( HNPCC ) was investigated .

[ { "offsets": [ 129, 171 ], "text": "hereditary non - polyposis cancer syndrome", "type": "Disease" }, { "offsets": [ 174, 179 ], "text": "HNPCC", "type": "Disease" } ]

The mutation ( A - - > T at nt943 + 3 ) disrupts the 3 splice site of exon 5 leading to the deletion of this exon from MSH2 mRNA and represents the only frequent MSH2 mutation so far reported .

[]

Although this mutation was initially detected in four of 33 colorectal cancer families analysed from eastern England , more extensive analysis has reduced the frequency to four of 52 ( 8 % ) English HNPCC kindreds analysed .

[ { "offsets": [ 60, 77 ], "text": "colorectal cancer", "type": "Disease" }, { "offsets": [ 199, 204 ], "text": "HNPCC", "type": "Disease" } ]

In contrast , the MSH2 mutation was identified in 10 of 20 ( 50 % ) separately identified colorectal families from Newfoundland .

[ { "offsets": [ 90, 100 ], "text": "colorectal", "type": "Disease" } ]

To investigate the origin of this mutation in colorectal cancer families from England ( n = 4 ) , Newfoundland ( n = 10 ) , and the United States ( n = 3 ) , haplotype analysis using microsatellite markers linked to MSH2 was performed .

[ { "offsets": [ 46, 63 ], "text": "colorectal cancer", "type": "Disease" } ]

Within the English and US families there was little evidence for a recent common origin of the MSH2 splice site mutation in most families .

[]

In contrast , a common haplotype was identified at the two flanking markers ( CA5 and D2S288 ) in eight of the Newfoundland families .

[]

These findings suggested a founder effect within Newfoundland similar to that reported by others for two MLH1 mutations in Finnish HNPCC families .

[ { "offsets": [ 131, 136 ], "text": "HNPCC", "type": "Disease" } ]

We calculated age related risks of all , colorectal , endometrial , and ovarian cancers in nt943 + 3 A - - > T MSH2 mutation carriers ( n = 76 ) for all patients and for men and women separately .

[ { "offsets": [ 41, 87 ], "text": "colorectal , endometrial , and ovarian cancers", "type": "Disease" } ]

For both sexes combined , the penetrances at age 60 years for all cancers and for colorectal cancer were 0 .

[ { "offsets": [ 66, 73 ], "text": "cancers", "type": "Disease" }, { "offsets": [ 82, 99 ], "text": "colorectal cancer", "type": "Disease" } ]

86 and 0 .

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57 , respectively .

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The risk of colorectal cancer was significantly higher ( p < 0 . 01 ) in males than females ( 0 . 63 v 0 . 30 and 0 . 84 v 0 . 44 at ages 50 and 60 years , respectively ) .

[ { "offsets": [ 12, 29 ], "text": "colorectal cancer", "type": "Disease" } ]

For females there was a high risk of endometrial cancer ( 0 . 5 at age 60 years ) and premenopausal ovarian cancer ( 0 . 2 at 50 years ) .

[ { "offsets": [ 37, 55 ], "text": "endometrial cancer", "type": "Disease" }, { "offsets": [ 86, 114 ], "text": "premenopausal ovarian cancer", "type": "Disease" } ]

These intersex differences in colorectal cancer risks have implications for screening programmes and for attempts to identify colorectal cancer susceptibility modifiers .

[ { "offsets": [ 30, 47 ], "text": "colorectal cancer", "type": "Disease" }, { "offsets": [ 126, 143 ], "text": "colorectal cancer", "type": "Disease" } ]

Age of onset in Huntington disease : sex specific influence of apolipoprotein E genotype and normal CAG repeat length .

[ { "offsets": [ 16, 34 ], "text": "Huntington disease", "type": "Disease" } ]

Age of onset ( AO ) of Huntington disease ( HD ) is known to be correlated with the length of an expanded CAG repeat in the HD gene .

[ { "offsets": [ 23, 41 ], "text": "Huntington disease", "type": "Disease" }, { "offsets": [ 44, 46 ], "text": "HD", "type": "Disease" }, { "offsets": [ 124, 126 ], "text": "HD", "type": "Disease" } ]

Apolipoprotein E ( APOE ) genotype , in turn , is known to influence AO in Alzheimer disease , rendering the APOE gene a likely candidate to affect AO in other neurological diseases too .

[ { "offsets": [ 75, 92 ], "text": "Alzheimer disease", "type": "Disease" }, { "offsets": [ 160, 181 ], "text": "neurological diseases", "type": "Disease" } ]

We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length .

[ { "offsets": [ 74, 76 ], "text": "HD", "type": "Disease" }, { "offsets": [ 90, 92 ], "text": "HD", "type": "Disease" } ]

Genotyping for APOE was performed blind to clinical information .

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In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients , we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females .

[ { "offsets": [ 99, 101 ], "text": "HD", "type": "Disease" } ]

Such a sex difference in AO was not apparent for any of the other APOE genotypes .

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Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO .

[ { "offsets": [ 66, 83 ], "text": "neurodegeneration", "type": "Disease" }, { "offsets": [ 87, 89 ], "text": "HD", "type": "Disease" } ]

Familial deficiency of the seventh component of complement associated with recurrent bacteremic infections due to Neisseria .

[ { "offsets": [ 0, 58 ], "text": "Familial deficiency of the seventh component of complement", "type": "Disease" }, { "offsets": [ 85, 123 ], "text": "bacteremic infections due to Neisseria", "type": "Disease" } ]

The serum of a 29 - year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity .

[ { "offsets": [ 60, 93 ], "text": "disseminated gonococcal infection", "type": "Disease" }, { "offsets": [ 111, 135 ], "text": "meningococcal meningitis", "type": "Disease" }, { "offsets": [ 140, 149 ], "text": "arthritis", "type": "Disease" } ]

The seventh component of complement ( C7 ) was not detected by functional or immunochemical assays , whereas other components were normal by hemolytic and immunochemical assessment .

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Her fresh serum lacked complement - mediated bactericidal activity against Neisseria gonorrhoeae , but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity .

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The absence of functional C7 activity could not be accounted for on the basis of an inhibitor .

[ { "offsets": [ 4, 28 ], "text": "absence of functional C7", "type": "Disease" } ]

Opsonization and generation of chemotactic activity functioned normally .

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Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this siblings clinically well eight - year - old son .

[ { "offsets": [ 0, 22 ], "text": "Complete absence of C7", "type": "Disease" }, { "offsets": [ 86, 110 ], "text": "meningococcal meningitis", "type": "Disease" }, { "offsets": [ 115, 124 ], "text": "arthritis", "type": "Disease" } ]

HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci .

[ { "offsets": [ 104, 117 ], "text": "C7 deficiency", "type": "Disease" } ]

This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections .

[ { "offsets": [ 42, 55 ], "text": "C7 deficiency", "type": "Disease" }, { "offsets": [ 178, 209 ], "text": "bacteremic neisseria infections", "type": "Disease" } ]

Increased incidence of cancer in patients with cartilage - hair hypoplasia .

[ { "offsets": [ 23, 29 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 47, 74 ], "text": "cartilage - hair hypoplasia", "type": "Disease" } ]

OBJECTIVE Previous reports have suggested an increased risk of cancer among patients with cartilage - hair hypoplasia ( CHH ) .

[ { "offsets": [ 63, 69 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 90, 117 ], "text": "cartilage - hair hypoplasia", "type": "Disease" }, { "offsets": [ 120, 123 ], "text": "CHH", "type": "Disease" } ]

This study was carried out to further evaluate this risk among patients with CHH and their first - degree relatives .

[ { "offsets": [ 77, 80 ], "text": "CHH", "type": "Disease" } ]

STUDY DESIGN One hundred twenty - two patients with CHH were identified through 2 countrywide epidemiologic surveys in 1974 and in 1986 .

[ { "offsets": [ 52, 55 ], "text": "CHH", "type": "Disease" } ]

Their parents and nonaffected siblings were identified through the Population Register Center .

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This cohort underwent follow - up for cancer incidence through the Finnish Cancer Registry to the end of 1995 .

[ { "offsets": [ 38, 44 ], "text": "cancer", "type": "Disease" } ]

RESULTS A statistically significant excess risk of cancer was seen among the patients with CHH ( standardized incidence ratio 6 . 9 , 95 % confidence interval 2 . 3 to 16 ) , which was mainly attributable to non - Hodgkins lymphoma ( standardized incidence ratio 90 , 95 % confidence interval 18 to 264 ) .

[ { "offsets": [ 51, 57 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 91, 94 ], "text": "CHH", "type": "Disease" }, { "offsets": [ 208, 231 ], "text": "non - Hodgkins lymphoma", "type": "Disease" } ]

In addition , a significant excess risk of basal cell carcinoma was seen ( standardized incidence ratio 35 , 95 % confidence interval 7 . 2 to 102 ) .

[ { "offsets": [ 43, 63 ], "text": "basal cell carcinoma", "type": "Disease" } ]

The cancer incidence among the siblings or the parents did not differ from the average cancer incidence in the Finnish population .

[ { "offsets": [ 4, 10 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 87, 93 ], "text": "cancer", "type": "Disease" } ]

CONCLUSIONS This study confirms an increased risk of cancer , especially non - Hodgkins lymphoma , probably attributable to defective immunity , among patients with CHH .

[ { "offsets": [ 53, 59 ], "text": "cancer", "type": "Disease" }, { "offsets": [ 73, 96 ], "text": "non - Hodgkins lymphoma", "type": "Disease" }, { "offsets": [ 165, 168 ], "text": "CHH", "type": "Disease" } ]

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency .

[ { "offsets": [ 40, 82 ], "text": "dihydropyrimidine dehydrogenase deficiency", "type": "Disease" } ]

Dihydropyrimidine dehydrogenase ( DPD ) deficiency is an autosomal recessive disease characterised by thymine - uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype .

[ { "offsets": [ 0, 50 ], "text": "Dihydropyrimidine dehydrogenase ( DPD ) deficiency", "type": "Disease" }, { "offsets": [ 57, 84 ], "text": "autosomal recessive disease", "type": "Disease" } ]

In order to understand the genetic and phenotypic basis for DPD deficiency , we have reviewed 17 families presenting 22 patients with complete deficiency of DPD .

[ { "offsets": [ 60, 74 ], "text": "DPD deficiency", "type": "Disease" }, { "offsets": [ 143, 160 ], "text": "deficiency of DPD", "type": "Disease" } ]

In this group of patients , 7 different mutations have been identified , including 2 deletions [ 295 - 298delTCAT , 1897delC ] , 1 splice - site mutation [ IVS14 + 1G > A ) ] and 4 missense mutations ( 85T > C , 703C > T , 2658G > A , 2983G > T ) .

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Analysis of the prevalence of the various mutations among DPD patients has shown that the G - - > A point mutation in the invariant splice donor site is by far the most common ( 52 % ) , whereas the other six mutations are less frequently observed .

[ { "offsets": [ 58, 61 ], "text": "DPD", "type": "Disease" } ]

A large phenotypic variability has been observed , with convulsive disorders , motor retardation and mental retardation being the most abundant manifestations .

[ { "offsets": [ 56, 76 ], "text": "convulsive disorders", "type": "Disease" }, { "offsets": [ 79, 96 ], "text": "motor retardation", "type": "Disease" }, { "offsets": [ 101, 119 ], "text": "mental retardation", "type": "Disease" } ]

A clear correlation between the genotype and phenotype has not been established .

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An altered beta - alanine , uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency .

[ { "offsets": [ 86, 108 ], "text": "clinical abnormalities", "type": "Disease" }, { "offsets": [ 138, 152 ], "text": "DPD deficiency", "type": "Disease" } ]

Fibroblast growth factor homologous factor 2 ( FHF2 ) : gene structure , expression and mapping to the Borjeson - Forssman - Lehmann syndrome region in Xq26 delineated by a duplication breakpoint in a BFLS - like patient .

[ { "offsets": [ 103, 141 ], "text": "Borjeson - Forssman - Lehmann syndrome", "type": "Disease" }, { "offsets": [ 201, 205 ], "text": "BFLS", "type": "Disease" } ]

Borjeson - Forssman - Lehmann syndrome ( BFLS ) is a syndromal X - linked mental retardation , which maps by linkage to the q26 region of the human X chromosome .

[ { "offsets": [ 0, 38 ], "text": "Borjeson - Forssman - Lehmann syndrome", "type": "Disease" }, { "offsets": [ 41, 45 ], "text": "BFLS", "type": "Disease" }, { "offsets": [ 63, 92 ], "text": "X - linked mental retardation", "type": "Disease" } ]

We have identified a male patient with BFLS - like features and a duplication , 46 , Y , dup ( X ) ( q26q28 ) , inherited from his phenotypically normal mother .

[ { "offsets": [ 39, 43 ], "text": "BFLS", "type": "Disease" } ]

Fluorescence in situ hybridisation using yeast artificial chromosome clones from Xq26 localised the duplication breakpoint to an approximately 400 - kb interval in the Xq26 .

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3 region between DXS155 and DXS294 / DXS730 .

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Database searches and analysis of available genomic DNA sequence from the region revealed the presence of the fibroblast growth factor homologous factor gene , FHF2 , within the duplication breakpoint interval .

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The gene structure of FHF2 was determined and two new exons were identified , including a new 5 end exon , 1B .

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FHF2 is a large gene extending over approximately 200 kb in Xq26 .

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3 and is composed of at least seven exons .

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It shows tissue - specific alternative splicing and alternative transcription starts .

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Northern blot hybridisation showed highest expression in brain and skeletal muscle .

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The FHF2 gene localisation and tissue - specific expression pattern suggest it to be a candidate gene for familial cases of the BFLS syndrome and other syndromal and non - specific forms of X - linked mental retardation mapping to the region .

[ { "offsets": [ 128, 141 ], "text": "BFLS syndrome", "type": "Disease" }, { "offsets": [ 190, 219 ], "text": "X - linked mental retardation", "type": "Disease" } ]

Germline E - cadherin gene ( CDH1 ) mutations predispose to familial gastric cancer and colorectal cancer .

[ { "offsets": [ 60, 83 ], "text": "familial gastric cancer", "type": "Disease" }, { "offsets": [ 88, 105 ], "text": "colorectal cancer", "type": "Disease" } ]

Inherited mutations in the E - cadherin gene ( CDH1 ) were described recently in three Maori kindreds with familial gastric cancer .

[ { "offsets": [ 107, 130 ], "text": "familial gastric cancer", "type": "Disease" } ]

Familial gastric cancer is genetically heterogeneous and it is not clear what proportion of gastric cancer susceptibility in non - Maori populations is due to germline CDH1 mutations .

[ { "offsets": [ 0, 23 ], "text": "Familial gastric cancer", "type": "Disease" }, { "offsets": [ 92, 106 ], "text": "gastric cancer", "type": "Disease" } ]

Therefore , we screened eight familial gastric cancer kindreds of British and Irish origin for germline CDH1 mutations , by SSCP analysis of all 16 exons and flanking sequences .

[ { "offsets": [ 30, 53 ], "text": "familial gastric cancer", "type": "Disease" } ]

Each family contained ( i ) two cases of gastric cancer in first degree relatives with one affected before age 50 years ; or ( ii ) three or more cases of gastric cancer .

[ { "offsets": [ 41, 55 ], "text": "gastric cancer", "type": "Disease" }, { "offsets": [ 155, 169 ], "text": "gastric cancer", "type": "Disease" } ]

Novel germline CDH1 mutations ( a nonsense and a splice site ) were detected in two families ( 25 % ) .

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Both mutations were predicted to truncate the E - cadherin protein in the signal peptide domain .

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In one family there was evidence of non - penetrance and susceptibility to both gastric and colorectal cancer ; thus , in addition to six cases of gastric cancer , a CDH1 mutation carrier developed colorectal cancer at age 30 years .

[ { "offsets": [ 80, 109 ], "text": "gastric and colorectal cancer", "type": "Disease" }, { "offsets": [ 147, 161 ], "text": "gastric cancer", "type": "Disease" }, { "offsets": [ 198, 215 ], "text": "colorectal cancer", "type": "Disease" } ]

We have confirmed that germline mutations in the CDH1 gene cause familial gastric cancer in non - Maori populations .

[ { "offsets": [ 65, 88 ], "text": "familial gastric cancer", "type": "Disease" } ]

However , only a minority of familial gastric cancers can be accounted for by CDH1 mutations .

[ { "offsets": [ 38, 53 ], "text": "gastric cancers", "type": "Disease" } ]

Loss of E - cadherin function has been implicated in the pathogenesis of sporadic colorectal and other cancers , and our findings provide evidence that germline CDH1 mutations predispose to early onset colorectal cancer .

[ { "offsets": [ 82, 110 ], "text": "colorectal and other cancers", "type": "Disease" }, { "offsets": [ 202, 219 ], "text": "colorectal cancer", "type": "Disease" } ]

Thus , CDH1 should be investigated as a cause of inherited susceptibility to both gastric and colorectal cancers .

[ { "offsets": [ 82, 112 ], "text": "gastric and colorectal cancers", "type": "Disease" } ]

A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys - Drash syndrome .

[ { "offsets": [ 69, 93 ], "text": "urogenital abnormalities", "type": "Disease" }, { "offsets": [ 97, 119 ], "text": "Denys - Drash syndrome", "type": "Disease" } ]

The Wilms tumor - suppressor gene , WT1 , plays a key role in urogenital development , and WT1 dysfunction is implicated in both neoplastic ( Wilms tumor , mesothelioma , leukemias , and breast cancer ) and nonneoplastic ( glomerulosclerosis ) disease .

[ { "offsets": [ 4, 15 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 91, 106 ], "text": "WT1 dysfunction", "type": "Disease" }, { "offsets": [ 129, 139 ], "text": "neoplastic", "type": "Disease" }, { "offsets": [ 142, 153 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 156, 168 ], "text": "mesothelioma", "type": "Disease" }, { "offsets": [ 171, 180 ], "text": "leukemias", "type": "Disease" }, { "offsets": [ 187, 200 ], "text": "breast cancer", "type": "Disease" }, { "offsets": [ 207, 220 ], "text": "nonneoplastic", "type": "Disease" }, { "offsets": [ 223, 241 ], "text": "glomerulosclerosis", "type": "Disease" } ]

The analysis of diseases linked specifically with WT1 mutations , such as Denys - Drash syndrome ( DDS ) , can provide valuable insight concerning the role of WT1 in development and disease .

[ { "offsets": [ 74, 96 ], "text": "Denys - Drash syndrome", "type": "Disease" }, { "offsets": [ 99, 102 ], "text": "DDS", "type": "Disease" } ]

DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis , XY pseudohermaphroditism , and / or Wilms tumor ( WT ) .

[ { "offsets": [ 0, 3 ], "text": "DDS", "type": "Disease" }, { "offsets": [ 51, 62 ], "text": "nephropathy", "type": "Disease" }, { "offsets": [ 73, 92 ], "text": "mesangial sclerosis", "type": "Disease" }, { "offsets": [ 98, 119 ], "text": "pseudohermaphroditism", "type": "Disease" }, { "offsets": [ 131, 142 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 145, 147 ], "text": "WT", "type": "Disease" } ]

DDS patients are constitutionally heterozygous for exonic point mutations in WT1 , which include mutations predicted to truncate the protein within the C - terminal zinc finger ( ZF ) region .

[ { "offsets": [ 0, 3 ], "text": "DDS", "type": "Disease" } ]

We report that heterozygosity for a targeted murine Wt1 allele , Wt1 ( tmT396 ) , which truncates ZF3 at codon 396 , induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice .

[ { "offsets": [ 125, 144 ], "text": "mesangial sclerosis", "type": "Disease" }, { "offsets": [ 163, 166 ], "text": "DDS", "type": "Disease" } ]

Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event , implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice .

[ { "offsets": [ 0, 20 ], "text": "Male genital defects", "type": "Disease" }, { "offsets": [ 70, 81 ], "text": "Wilms tumor", "type": "Disease" }, { "offsets": [ 197, 212 ], "text": "Wt1 dysfunction", "type": "Disease" }, { "offsets": [ 217, 236 ], "text": "Wilms tumorigenesis", "type": "Disease" } ]

However , the mutant WT1 ( tmT396 ) protein accounted for only 5 % of WT1 in both heterozygous embryonic stem cells and the WT .

[ { "offsets": [ 124, 126 ], "text": "WT", "type": "Disease" } ]

This has implications regarding the mechanism by which the mutant allele exerts its effect .

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Mechanism of increased iron absorption in murine model of hereditary hemochromatosis : increased duodenal expression of the iron transporter DMT1 .

[ { "offsets": [ 58, 84 ], "text": "hereditary hemochromatosis", "type": "Disease" } ]

Hereditary hemochromatosis ( HH ) is a common autosomal recessive disorder characterized by tissue iron deposition secondary to excessive dietary iron absorption .

[ { "offsets": [ 0, 26 ], "text": "Hereditary hemochromatosis", "type": "Disease" }, { "offsets": [ 29, 31 ], "text": "HH", "type": "Disease" }, { "offsets": [ 46, 74 ], "text": "autosomal recessive disorder", "type": "Disease" } ]

We recently reported that HFE , the protein defective in HH , was physically associated with the transferrin receptor ( TfR ) in duodenal crypt cells and proposed that mutations in HFE attenuate the uptake of transferrin - bound iron from plasma by duodenal crypt cells , leading to up - regulation of transporters for dietary iron .

[ { "offsets": [ 57, 59 ], "text": "HH", "type": "Disease" } ]

Here , we tested the hypothesis that HFE - / - mice have increased duodenal expression of the divalent metal transporter ( DMT1 ) .

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By 4 weeks of age , the HFE - / - mice demonstrated iron loading when compared with HFE + / + littermates , with elevated transferrin saturations ( 68 . 4 % vs . 49 . 8 % ) and elevated liver iron concentrations ( 985 micrograms vs . 381 micrograms ) .

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By using Northern blot analyses , we quantitated duodenal expression of both classes of DMT1 transcripts one containing an iron responsive element ( IRE ) , called DMT1 ( IRE ) , and one containing no IRE , called DMT1 ( non - IRE ) .

[]