Prevalence of HFE gene C282Y and H63D mutations in a French-Canadian population of neonates and in referred patients.

Hereditary hemochromatosis is a genetic disease characterized by exaggerated absorption of intestinal iron leading to its accumulation in some organs over the years. Its prevalence is estimated to be 3-5/1000 in Caucasians. A single mutation, C282Y in the HFE gene explains 80-90% of all diagnosed cases in populations of northwestern European ancestry. The importance of another frequent mutation in this gene, H63D, as well as of C282Y/H63D compound heterozygotes, is still a matter of debate. We estimated the prevalence of these mutations in newborns from a genetically well defined French-Canadian population, in Quebec City. We compared genotype and allele frequencies between neonates and referred patients for HFE molecular analysis. We genotyped anonymous-unlinked cord blood samples for C282Y (n = 881) and H63D (n = 870) mutations from neonates. Referred patients (n = 1084) were genotyped in two different laboratories and pooled after verifying the similarity of both groups. No C282Y homozygote was found in neonates (allele frequency = 0.043). However, we identified 163 C282Y homozygotes (15%) among 1084 referred patients leading to a, not surprising, 97-fold enrichment of this genotype. We found a similar proportion of genotypes homozygous for H63D in both groups suggesting a weak association with the disease. However, we found a 5-fold enrichment of compound heterozygotes in the referred group. Fewer C282Y homozygotes were observed in the French-Canadian population than in northwest Europe populations. However, the strong enrichment of homozygotes between the neonates and the referred patients is an argument in favour of screening for this lethal disease.