Mura et al. (1999) reported on the analysis of the cys282-to-tyr (C282Y; 613609.0001), his63-to-asp (H63D; 613609.0002), and ser65-to-cys (S65C) mutations of the HFE gene in a series of 711 probands with hereditary hemochromatosis (235200) and 410 controls. The results confirmed that the C282Y substitution is the main mutation involved in HH, accounting for 85% of carrier chromosomes, whereas the H63D substitution represented 39% of the HH chromosomes that did not carry the C282Y mutation. In addition, the screening showed that the S65C substitution, which results from a 193A-T transversion, was significantly enriched in probands with at least 1 chromosome without an assigned mutation. This substitution accounted for 7.8% of HH chromosomes that were neither C282Y nor H63D. This enrichment of S65C among HH chromosomes suggested that the S65C substitution is associated with a mild form of hemochromatosis.
Barton et al. (1999) identified the S65C mutation in 2 patients. One was also heterozygous for C282Y, i.e., was a compound heterozygote, and had porphyria cutanea tarda (see 176100). The other patient had hereditary stomatocytosis (185000). Iron overload due to the HFE mutations probably precipitated or exacerbated the porphyria cutanea tarda in the first patient. In the second patient, iron overload from the hereditary stomatocytosis undoubtedly exacerbated the iron overload due to the HFE mutation.
