title: A homozygous HAMP mutation in a multiply consanguineous family with pseudo-dominant juvenile hemochromatosis.
abstract: Juvenile hemochromatosis (JH) is an autosomal recessive condition that leads to significant morbidity due to early onset systemic iron overload. The majority of families with JH link to chromosome 1q and were recently found to have mutations in the HFE2 gene encoding hemojuvelin; however, several JH families have been reported to have mutations in the HAMP gene encoding hepcidin. Here, we report a multiply consanguineous family with a father and daughter showing iron overload consistent with JH. Sequence analysis of HAMP revealed homozygosity for amino acid substitution C78T due to a c.233G > A mutation. This mutation disrupts one of eight highly conserved cysteines that are believed to be critical for the function of the active enzyme. This finding adds support to the importance of the role of these conserved cysteines in the activity of hepcidin.
authors.affiliation: Bruce Lefroy Center for Genetic Health Research, Murdoch Childrens Research Institute, University of Melbourne, Department of Paediatrics, Parkville, Victoria, Australia. martin.delatycki@ghsv.org.au
authors.forename: M B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: K J
authors.initials: KJ
authors.lastname: Allen
authors.forename: P
authors.initials: P
authors.lastname: Gow
authors.forename: J
authors.initials: J
authors.lastname: MacFarlane
authors.forename: C
authors.initials: C
authors.lastname: Radomski
authors.forename: J
authors.initials: J
authors.lastname: Thompson
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Y P
authors.initials: YP
authors.lastname: Goldberg
authors.forename: M E
authors.initials: ME
authors.lastname: Samuels
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D005260:Female; D005799:Genes, Dominant; D006432:Hemochromatosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D064451:Hepcidins; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008967:Molecular Biology; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins