HFE polymorphism in German patients with hereditary haemochromatosis

Background and objective: Hereditary haemochromatosis (HH) is the most comm on genetically determined disease of the white population which by iron ove rload causes multiorgan functional impairment. Recently the gene for HH (HF E gene) has been located on chromosome 6. The development of HH is thought to be caused by two point mutations that lead to an aminoacid exchange of t yrosine for cysteine on codon 282 (Cys282Tyr) and of histidine by aspargic acid on codon 63 (His63Asp). Patients and methods: 75 patients with phenotypically confirmed HH were exa mined genetically. The analysis of the HFE-gene mutation was done on genomi c DNA by restriction digestion with the restriction enzymes Rsal and Mbol. Results: Homozygosity for the Cys282Tyr mutation was found in 66 (88%) of t he patients, while two were heterozygous. Of seven patients with wild-type sequence of the aminoacid position 282, three (43%) had a His63Asp exchange . Overall only four patients had neither of the two mutations. Conclusions: Because of different geographical distributions, a knowledge o f the mutation rate is important for patients with HH. to assess the diagno stic value of the gene test. For the first time gene analysis makes it poss ible to diagnose HH before clinically significant iron overload occurs. It may further improve prognosis of the disease by early application of therap eutic blood-letting.