Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred.
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.
Specktor
Polina
P
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.
Cooper
John G
JG
Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
Indelman
Margarita
M
Department of Dermatology, Laboratory of Molecular Dermatology, Rambam Medical Center, POB 9602, 31096, Haifa, Israel.
Sprecher
Eli
E
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.
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
D018389:Codon, Nonsense; D000089703:Fibroblast Growth Factor-23; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human