A candidate gene for hemochromatosis: frequency of the C282Y and H63D mutations

Jouanolle, A. M.; Fergelot, Patricia; Gandon, G.; Yaouanq, J.; Gall, J. Y. Le; David, Véronique

doi:10.1007/s004390050549

Cited by 112 publications

(55 citation statements)

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“…These findings are different from those reported for Northern Europe, where more than 90% of the patients are C282Y homozygotes or C282Y and H63D compound heterozygotes (5,(20)(21)(22)(23)(24)(25), but agree with recent data reported for Italy, where approximately one third of the patients with HH showed neither C282Y or H63D mutations, nor any other mutation in the HFE gene by sequence analysis (26)(27)(28). Similarly, none of these mutations were detected in African Americans with HH or in subjects with African iron overload, another hereditary disorder of iron metabolism that is much more heterogeneous than HH (12,13).…”

Section: Discussioncontrasting

confidence: 86%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

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Couto

et al. 2002

Braz J Med Biol Res

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The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.

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Section: Discussioncontrasting

confidence: 86%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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“…1 Worldwide, 69% to 100% of patients with typical phenotypic hemochromatosis are C282Y homozygotes. [1][2][3][4][5][6] In referral centers, within pedigrees with iron overload, close to 100% of typical patients are C282Y homozygotes. 1,4 Genetic testing has thus replaced liver biopsy in the diagnosis of hemochromatosis in many C282Y homozygotes.…”

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confidence: 99%

Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis

Beaton

2002

Hepatology

130

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The aim of the present study was to examine the predictive accuracy of noninvasive clinical and biochemical variables associated with cirrhosis among patients with C282Y homozygous hemochromatosis. Sixteen clinical and laboratory variables were recorded at the time of diagnosis in 193 Canadian C282Y homozygous patients. All patients underwent percutaneous liver biopsy and 27 (14%) had biopsy specimen-proven cirrhosis. Prediction of cirrhosis was assessed first by univariate regression analysis. Variables significantly related to cirrhosis were then evaluated by stepwise linear multivariate regression. Receiver operating characteristic curve analysis of the most informative variables from multivariate analysis was then used to devise a clinically applicable index for the noninvasive prediction of cirrhosis. This index was then validated in 162 C282Y homozygous patients in France. Ferritin, blood platelets, and aspartate transaminase (AST) level were selected for the clinical index. The combination of ferritin levels of 1,000 g/L or greater, platelet levels of 200 ؋ 10 9 /L or less, and AST levels above the upper limit of normal led to a correct diagnosis of cirrhosis in 77% of Canadian patients. In the French patients, this led to a correct diagnosis of cirrhosis in 90%. In conclusion, in C282Y homozygous patients, a combination of easily measured laboratory variables (ferritin, platelets, AST) can be used to make the diagnosis of cirrhosis in approximately 81% of cases, reducing the need for liver biopsy. (HEPATOLOGY 2002;36: 673-678.)

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“…Studies in well-defined pedigrees have demonstrated that 83% to 100% of typical hemochromatosis patients have a missense mutation in the HFE gene that results in a cysteine-to-tyrosine substitution at codon 282 (C282Y). [4][5][6] Hemosiderosis is a common finding in nonbiliary causes of cirrhosis. It has been postulated that at least part of the explanation for this phenomenon is heterozygosity for the C282Y mutation.…”

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confidence: 99%