title: A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification.
abstract: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC; MIM211900) is a rare autosomal recessive disorder characterized by the progressive deposition of calcified masses in cutaneous and subcutaneous tissues, associated with elevated circulating levels of phosphate. The disease was initially found to result from mutations in GALNT3 encoding a glycosyltransferase. However, more recently, the S71G missense mutation in FGF23, encoding a potent phosphaturic protein, was identified in two families. In the present report, we describe a second mutation in FGF23 underlying a severe case displaying calcifications of cutaneous and numerous extracutaneous tissues. The mutation (M96T) was found to affect a highly conserved methionine residue at position 96 of the protein. These observations illustrate the extent of genetic and phenotypic heterogeneity in HFTC.
authors.affiliation: Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, 9602, Haifa, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Chefetz
authors.forename: Raoul
authors.initials: R
authors.lastname: Heller
authors.forename: Assimina
authors.initials: A
authors.lastname: Galli-Tsinopoulou
authors.forename: Gabriele
authors.initials: G
authors.lastname: Richard
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Friederike
authors.initials: F
authors.lastname: Koerber
authors.forename: Orit
authors.initials: O
authors.lastname: Topaz
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Eckhard
authors.initials: E
authors.lastname: Schoenau
mesh_terms: D019943:Amino Acid Substitution; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human