title: Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred.
abstract: Hyperphosphatemic familial tumoral calcinosis (HFTC) is an autosomal recessive metabolic disorder characterized by extensive phenotypic and genetic heterogeneity. HFTC was shown recently to result from mutations in two genes: GALNT3, coding for a glycosyltransferase responsible for initiating O-glycosylation, and FGF23, coding for a potent phosphaturic protein. All GALNT3 mutations reported so far have been identified in patients of either Middle Eastern or African-American extraction, corroborating numerous historical reports of the disorder in Africa and in the Middle East. In the present study, we describe a patient of Northern European origin displaying typical features of HFTC. Mutation analysis revealed that this patient carries a homozygous novel nonsense mutation in GALNT3 predicted to result in the synthesis of a significantly truncated protein. The present results expand the spectrum of known mutations in GALNT3 and demonstrate the existence of HFTC-causing mutations in this gene outside the Middle Eastern and African-American populations.
authors.affiliation: Department of Dermatology, Laboratory of Molecular Dermatology, Rambam Medical Center, POB 9602, 31096, Haifa, Israel.|Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Polina
authors.initials: P
authors.lastname: Specktor
authors.affiliation: Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: John G
authors.initials: JG
authors.lastname: Cooper
authors.affiliation: Department of Dermatology, Laboratory of Molecular Dermatology, Rambam Medical Center, POB 9602, 31096, Haifa, Israel.
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.affiliation: Department of Dermatology, Laboratory of Molecular Dermatology, Rambam Medical Center, POB 9602, 31096, Haifa, Israel. e_sprecher@rambam.health.gov.il.|The Rappaport Family Institute for Research in the Medical Sciences, 31096, Haifa, Israel. e_sprecher@rambam.health.gov.il.|Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. e_sprecher@rambam.health.gov.il.
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D000328:Adult; D001483:Base Sequence; D002114:Calcinosis / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D018389:Codon, Nonsense; D000089703:Fibroblast Growth Factor-23; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human