title: A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin.
abstract: The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, University of Rostock, Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Steiner
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ocran
authors.forename: Janine
authors.initials: J
authors.lastname: Genschel
authors.forename: Patrick
authors.initials: P
authors.lastname: Meier
authors.forename: Helga
authors.initials: H
authors.lastname: Gerl
authors.forename: Michael
authors.initials: M
authors.lastname: Ventz
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Schneider
authors.forename: Carsten
authors.initials: C
authors.lastname: Büttner
authors.forename: Kamilla
authors.initials: K
authors.lastname: Wadowska
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kerner
authors.forename: Peter
authors.initials: P
authors.lastname: Schuff-Werner
authors.forename: Herbert
authors.initials: H
authors.lastname: Lochs
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
mesh_terms: D044466:Asian People; D004252:DNA Mutational Analysis; D005192:Family Health; D005858:Germany; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000208:ethnology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D019683:Penetrance; D022821:RNA Splice Sites / Q000235:genetics*; D014744:Vietnam / Q000208:ethnology
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D022821:RNA Splice Sites