Polymorphisms in the HFE gene

Hereditary hemochromatosis is an autosomal recessive disease characterized by progressive iron overload. Recently, a candidate gene named HFE was isol ated on the short arm of the chromosome 6 within which two mutations were i dentified: C282Y and H63D. To date, only homozygosity for the C282Y mutatio n is considered as a diagnostic criterion of hemochromatosis. 7.6% of the p atients studied in our laboratory did not carry two copies of the C282Y mut ation. On the other hand, a dysmetabolic iron overload syndrome has recentl y been described and the search for the C282Y and H63D mutations revealed t hat none of the patients was homozygous for C282Y while 67% exhibited one o f the mutations. The possibility of a new mutation in the HFE gene has been raised to explain the disease in the remaining patients, as well as, in th e few hemochromatotic patients without two copies of the C282Y mutation. Th e aim of this study was to search for new mutations in the HFE gene in 16 s uch patients. Direct sequencing of exons and 3 introns did not reveal any n ew mutation but identified a few polymorphisms.