Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective hybridization of small intestine and liver cDNA libraries was carried out using yeast artificial chromosomes (YACs) surrounding D6S105, the microsatellite that appears to be close to the gene for hereditary hemochromatosis (HFE). Of 14 candidate probes hybridizing with these YACs, only one, designated. LD5-1, detected abnormalities in southern blots of patients with hemochromatosis. Two different abnormalities. were detected in 3 of 55 patients with hemochromatosis with the LD5-1 probe, and one of these was detected in one of 44 normal subjects. The gene that hybridizes with this probe is located about 300-400 kb centromeric of D6S105. It is transcribed into mRNA that is about 8.5 kb in length in many tissues, including peripheral blood leukocytes. The available sequence indicates tha it codes for a zinc finger protein. We propose that there is a reasonable probability that LD5-1 hybridizes with the gene for hereditary hemochromatosis.
Blood Cells Mol Dis 1995
PMID:A strategy for cloning the hereditary hemochromatosis gene. 867 73

Hereditary hemochromatosis is a common disorder in people of European origin. The HLA-H gene has been found to have two mutations that apparently cause hemochromatosis. The principal mutation, 845G-->A (C282Y), is believed to have arisen relatively recently in the Celtic population. To determine the incidence of this mutation and the other hemochromatosis-associated mutation, 187C-->G (H63D), among Ashkenazi Jews, a people who are believed to have arrived in Europe in about the 8th Century A.D., we have examined the DNA from 381 unrelated Jewish subjects and 206 non-Jewish white controls. The gene frequency for the 845G-->A mutation among Jewish subjects was only 0.013 compared with a frequency of 0.070 among controls, a difference that is significant at the 0.00001 level. The phenotypically milder nt 187C-->G mutation had a frequency of 0.155 in the non-Jewish population and 0.097 in the Jewish population, a difference that was also statistically significant at the <0.01 level.
Blood Cells Mol Dis 1997
PMID:HLA-H mutations in the Ashkenazi Jewish population. 921 54

This report assesses the degree of iron overload in a cohort of patients in relationship to the presence or absence of the recently described 845 G-->A (C282Y) and 187 C-->G (H63D) mutations in the HFE (HLA-H) gene. Sixty-one patients with hereditary hemochromatosis diagnosed either with liver biopsy or on clinical grounds were included in this analysis. Forty-one patients were homozygous for C282Y, the genotype considered to be characteristic of hereditary hemochromatosis. At the time of this analysis, 37 of these 41 patients had achieved a state of iron depletion and mobilizable iron was calculated: 19 had less than 4 grams. Twenty-five of these 41 patients had liver biopsies; 4 of these patients had a hepatic iron index less than 1.9. Of the 4 patients with a normal hepatic iron index, 3 had a quantitative hepatic iron of greater than 50 micromol/g dry weight, and one had an inadequate biopsy sample. These findings support our suspicion that individuals may have hereditary hemochromatosis and homozygous C282Y despite relatively low body iron stores. Five patients were compound heterozygotes for C282Y and H63D. Four of these patients underwent liver biopsy; two had a hepatic iron index greater than 1.9. a third patient had a hepatic iron index of 1.3 but a quantitative hepatic iron of 90.6 micromol/g dry weight. All patients were phlebotomized to a state of iron depletion and only one of these patients had a mobilizable iron greater than 4 grams. Three patients were homozygous for H63D; these patients had either a hepatic iron index >1.9 or greater than 4 grams of mobilizable iron. Patients with homozygous H63D and significant iron overload are not well described. Seven patients were heterozygous for either C282Y or H63D; 4 had significant iron overload but three did not. Five patients had no HFE mutations; one of these patients unequivocally has iron overload with a hepatic iron index of 4.4 We conclude that: (1) Identification of HFE mutations will be clinically useful in identifying patients with hereditary hemochromatosis, (2) Patient genotyping will help confirm a diagnosis of hereditary hemochromatosis in some patients with relatively low body iron stores, (3) Significant iron loading can occur in the absence of homozygous C282Y, adding to the evidence that genes other than HFE may be involved in iron loading, and (4) Homozygous H63D can be associated with significant iron overload.
Blood Cells Mol Dis 1997 Aug
PMID:Correlation between genotype and phenotype in hereditary hemochromatosis: analysis of 61 cases. 941 Apr 75

Hereditary haemochromatosis is a common genetic disorder that causes hyperabsorption of dietary iron, leading to increased deposition and various organic diseases. Early diagnosis is important if effective treatment is to be applied and the iron overload corrected before the onset of clinical symptoms. Recently, a candidate gene has been identified in which a single point mutation shows a very close association with hereditary haemochromatosis. A polymerase chain reaction method using sequence specific primers (PCR-SSP) is described that, in conjunction with a simple DNA extraction method, would provide a specific diagnostic test or rapid screening procedure for this putative haemochromatosis associated mutation.
Mol Pathol 1997 Oct
PMID:A PCR-SSP method for detecting the Cys282Tyr mutation in the HFE gene associated with hereditary haemochromatosis. 949 21

Hereditary hemochromatosis mutation 845A (C282Y) in the HFE gene was recently described, and the C282Y frequencies were reported for various world populations. The aim of this study was to determine the Y allele frequencies of the C282Y mutation for five French populations. The most elevated value (= 5.6%) was obtained for Bretons, in accordance to the hypothesis indicating a Celtic origin of the hereditary hemochromatosis mutation.
Blood Cells Mol Dis 1998 Jun
PMID:Frequency of the C282Y mutation of hemochromatosis in five French populations. 964 97

Sixty patients diagnosed with hereditary hemochromatosis with grade 3 or 4 hepatic iron overload and 18 patients diagnosed with hereditary hemochromatosis who had less than grade 3 hepatic iron overload were examined for the HFE gene mutations, 845A (C282Y) and 187G (H63D). Control samples were obtained from 109 randomly selected individuals. Fifty-six of 60 unrelated hereditary hemochromatosis patients (93%) with grade 3 or 4 hepatic iron deposition were homozygous for the C282Y mutation. Fourteen of the 18 hereditary hemochromatosis patients with <3+ iron deposition (76%) were homozygous for the C282Y mutation. Three of 8 patients who were heterozygous for the C282Y mutation were also heterozygous for the H63D mutation. Thirty-one of 109 control individuals were heterozygous for the C282Y mutation and 27 were heterozygous for the H63D mutation. Our finding that 93% of hereditary hemochromatosis patients who fulfil standard diagnostic criteria are homozygous for the C282Y mutation provides clear evidence that this mutation is strongly associated with hereditary hemochromatosis. The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.
Blood Cells Mol Dis 1998 Dec
PMID:Hemochromatosis in Ireland and HFE. 985 96

The C282Y mutation in the HFE gene is the main mutation causing hemochromatosis, and C282Y frequencies have been reported for various European populations. The aim of this review is to compile the Y allele frequencies of the C282Y mutation for twenty European populations. The most elevated value (6.88%) is observed in residual Celtic populations in UK and France, in accordance to the hypothesis of Simon et al. concerning a Celtic origin of the hereditary hemochromatosis mutation.
Blood Cells Mol Dis 1998 Dec
PMID:Celtic origin of the C282Y mutation of hemochromatosis. 985 97

Hereditary haemochromatosis is an autosomal recessive disease in which there is defective regulation of iron absorption, causing gradual accumulation of excessive amounts of iron in certain organs. Recently, a candidate gene for hereditary haemochromatosis has been identified, located on the short arm of chromosome 6, telomeric to the major histocompatibility complex (MHC) and showing sequence homology to the human leucocyte antigen (HLA) class I genes. Two mutations have been found in this gene that are potential markers for haemochromatosis. The first, a cysteine to tyrosine substitution (Cys282Tyr) is strongly associated with the disease, whereas the second mutation, a histidine to aspartic acid substitution (His63Asp) shows a less obvious relation. To examine the importance of this second mutation in hereditary haemochromatosis it is important to study the links between this genotype and abnormalities of iron metabolism. A polymerase chain reaction method using sequence specific primers is described which might be useful for identifying those individuals carrying the mutation that encodes the His63Asp substitution, who might be at risk from a milder form of haemochromatosis.
Mol Pathol 1998 Aug
PMID:A PCR-SSP method for detecting the His63Asp mutation in the HFE gene associated with hereditary haemochromatosis. 989 53

The Cys282-->Tyr mutation in the HFE gene is carried by the majority of hereditary hemochromatosis patient chromosomes, yet some patients do not seem to harbor any mutation in this gene. This suggests a possibility that these patients may have a mutation in other genes in the same pathway as HFE. We analyzed the cDNA sequences of transferrin receptor (TFR), which was recently shown to interact with HFE, in twenty-one hereditary hemochromatosis patients including sixteen individuals who did not carry a Cys282-->Tyr mutation. A nucleotide substitution (424A-->G), which resulted in the Ser142-->Gly amino acid substitution, was the only amino acid polymorphism detected in the open reading frame of the TFR gene in these patients. This amino acid substitution was a rather common polymorphism in the general population (49%) and its frequency did not significantly differ in the hereditary hemochromatosis (HH) patients regardless of the HFE genotype. Thus, amino acid changes in the TFR gene do not appear to play a role in HH even when the patients do not have a HFE mutation. However, this study does not rule out the possibility of the involvement of mutations in non-coding regions.
Blood Cells Mol Dis 1998 Sep
PMID:Transferrin receptor mutation analysis in hereditary hemochromatosis patients. 1008 90

HFE is a non-typical MHC class 1-type protein that is mutated in hereditary hemochromatosis. The purpose of this study was to identify possible splice variants of HFE mRNA and investigate the regulation of these isoforms in duodenum and liver of patients with normal and altered iron stores. RT-PCR was performed using HFE specific primers and duodenal RNA obtained from patients with hemochromatosis, iron deficiency, secondary iron overload and normal controls. The reaction products were visualized by Southern blot and identified by DNA sequence analysis. Additional studies were performed on RNA isolated from liver and a range of human tissues. A truncated (soluble) form of HFE protein was identified that lacks the transmembrane domain and occurs as a result of alternative splicing. Soluble HFE was found predominantly in the duodenum, spleen, breast, skin and testicle. In hereditary hemochromatosis full length HFE was the predominant isoform present in the duodenum similar to iron deficiency. Alternate splicing produces soluble HFE that may have a unique function to regulate cellular iron transport.
Blood Cells Mol Dis 1999 Feb
PMID:Alternate splicing produces a soluble form of the hereditary hemochromatosis protein HFE. 1034 14


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