title: Hemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda.
abstract: Patients with porphyria cutanea tarda (PCT) reveal a susceptibility to reversible inactivation of hepatic uroporphyrinogen decarboxylase, which might be triggered by alcohol, hepatitis C virus infection, and iron overload. Inherited factors that may predispose to clinically overt PCT also include sequence deviations in the HFE gene that is mutated in classical hemochromatosis. Here, we studied the prevalence of both common and rare hemochromatosis gene variations in 51 PCT patients and 54 healthy controls of German origin. The frequency of the common HFE gene mutation C282Y was 15.7 % in PCT patients and 2.8 % in healthy control individuals (P < 0.001). By contrast, the frequencies of the common H63D mutation did not differ, and the allele frequencies of the less frequently observed sequence deviations as substitution S65C in the HFE gene and mutation Y250X in the TFR2 gene underlying hemochromatosis type 3 (HFE3) were < 0.02 both in PCT patients and controls. Our results comprise the first molecular studies of both common and rare hemochromatosis gene variants in German PCT patients, indicating a significant role of the C282Y mutation in the pathogenesis of PCT.
authors.affiliation: Department of Dermatology, University Hospital Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Frank
authors.forename: P
authors.initials: P
authors.lastname: Poblete-Gutiérrez
authors.forename: R
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: O
authors.initials: O
authors.lastname: Gressner
authors.forename: H F
authors.initials: HF
authors.lastname: Merk
authors.forename: F
authors.initials: F
authors.lastname: Lammert
mesh_terms: D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D017119:Porphyria Cutanea Tarda / Q000235:genetics* / Q000473:pathology; D011990:Receptors, Transferrin / Q000235:genetics; D013696:Temperature
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human