H63D is an haemochromatosis associated allele

[...]there is compelling evidence that the H63D allele is associated with HHC. 1-12 To evaluate the association of H63D with haemochromatosis, one must first recognise that H63D and C282Y are independent mutations of theHFE gene. Because the C282Y mutation is so common and is highly penetrant, homozygous C282Y predominates among cases of haemochromatosis, and H63D is not observed in C282Y homozygotes. In this re-analysis, we have compared the frequency of homozygous H63D, of which approximately 50 cases have now been described (a third with clinically significant iron overload), with the combined frequencies of homozygous C282C (that is, homozygous normal) and heterozygous H63D (that is, C282C/H63D), in random controls and patients with haemochromatosis, after exclusion of all cases that have C282Y. [...]we have tested the effect of H63D independently of any effect that might be observed in cases that also have C282Y.