title: Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis.
abstract: Ectopic periarticular calcifications associated with elevated levels of serum phosphate represent the principal clinical features of hyperphosphatemic familial tumoral calcinosis (HFTC), a rare autosomal recessive metabolic disorder. The disease can be caused by recessive mutations in at least two different genes: GalNAc transferase 3 (GALNT3), encoding a glycosyltransferase that initiates mucin-type O-glycosylation, and fibroblast growth factor 23 (FGF23), which encodes a regulator of phosphate circulating levels. In the current study, we performed mutation analyses of the GALNT3 gene in a subject with HFTC and in his relatives. Sequence analyses revealed that the proband was a compound heterozygote for two novel nonsense mutations in exon 4 (Y322X) and in exon 7 (Q481X). Cosegregation of the mutations with the disease within the family was confirmed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. This is the first report describing the simultaneous presence of two different stop codons in the coding sequence of the GALNT3 gene.
authors.affiliation: Department of Medical Sciences, Endocrine and Metabolic Unit, Pad. Granelli, University of Milan, Fondazione Policlinico IRCCS, Via Francesco Sforza 35, 20122, Milan, Italy. anna.barbieri@unimi.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Barbieri
authors.affiliation: Department of Medical Sciences, Endocrine and Metabolic Unit, Pad. Granelli, University of Milan, Fondazione Policlinico IRCCS, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Filopanti
authors.affiliation: Servizio di Neurologia, Policlinico Sassarese, Sassari, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Bua
authors.affiliation: Department of Medical Sciences, Endocrine and Metabolic Unit, Pad. Granelli, University of Milan, Fondazione Policlinico IRCCS, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
mesh_terms: D002114:Calcinosis / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000235:genetics*; D007558:Italy; D008297:Male; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; 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