[Demonstration of HFE polymorphism in German patients with hereditary hemochromatosis].
OBJECTIVE
Hereditary haemochromatosis (HH) is the most common genetically determined disease of the white population which by iron overload causes multiorgan functional impairment. Recently the gene for HH (HFE gene) has been located on chromosome 6. The development of HH is thought to be caused by two point mutations that lead to an amino acid exchange of tyrosine for cysteine on codon 282 (Cys282Tyr) and of histidine by aspargic acid on codon 63 (His63Asp).


METHODS
75 patients with phenotypically confirmed HH were examined genetically. The analysis of the HFE-gene mutation was done on genomic DNA by restriction digestion with the restriction enzymes Rsal and Mbol.


RESULTS
Homozygosity for the Cys282Tyr mutation was found in 66 (88%) of the patients, while two were heterozygous. Of seven patients with wild-type sequence of the amino acid 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 of the mutation rate is important for patients with HH. to assess the diagnostic value of the gene test. For the first time gene analysis makes it possible to diagnose HH before clinically significant iron overload occurs. It may further improve prognosis of the disease by early application of therapeutic blood-letting.
Erhardt
A
A
Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf. andreas.erhardt@uni-duesseldorf-de
Niederau
C
C
Osman
Y
Y
Hassan
M
M
Häussinger
D
D
D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D005858:Germany / Q000453:epidemiology; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D006579:Heterozygote; D006639:Histidine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D014443:Tyrosine / Q000235:genetics
D003062:Codon; D006680:HLA Antigens; D014443:Tyrosine; D006639:Histidine; D001216:Asparagine; D003545:Cysteine