Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis.
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.
Barbieri
Anna Maria
AM
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.
Filopanti
Marcello
M
Department of Medical Sciences, Endocrine and Metabolic Unit, Pad. Granelli, University of Milan, Fondazione Policlinico IRCCS, Via Francesco Sforza 35, 20122, Milan, Italy.
Bua
Guido
G
Servizio di Neurologia, Policlinico Sassarese, Sassari, Italy.
Beck-Peccoz
Paolo
P
Department of Medical Sciences, Endocrine and Metabolic Unit, Pad. Granelli, University of Milan, Fondazione Policlinico IRCCS, Via Francesco Sforza 35, 20122, Milan, Italy.
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
D018389:Codon, Nonsense; D000089703:Fibroblast Growth Factor-23; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human