Intron 2 [IVS2, T-C +4] HFE gene mutation associated with S65C causes alternative RNA splicing and is responsible for iron overload.

Unlabelled: A patient with congenital liver fibrosis revealed a high transferrin saturation index and iron overload on liver biopsy. He did not carry the most frequent HFE mutations: C282Y or H63D. Heterozygosity was detected for S65C. Unknown HFE mutations were also sought using a combined denaturing high performance liquid chromatography (DHPLC)/direct sequence approach and another point mutation, a transition T-C (nt 4910), at the fourth base of the donor splice site of intron 2 [HFE, intervening sequence (IVS) 2, T-C +4] was found. Family screening revealed that a daughter carried both S65C and [IVS2, T-C +4].

Conclusion: : The existence in our proband of a partly-altered HFE protein in the region encoded by exon 2 might be responsible for the histologically-demonstrated iron overload.