title: An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation.
abstract: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disease, characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D(3) (calcitriol) levels. This syndrome involves rickets with bone deformities in childhood and osteomalacia, osteoporosis, articular and para-articular pain, and fatigue in adulthood. It is caused by mutations in a consensus sequence for proteolytic cleavage of the FGF23 protein. Normally, this protein actively regulates phosphate homeostasis. Here we report a Tunisian family in which one parent and three children show clinical and biological features of ADHR. Mutation analysis of the FGF23 gene finds a heterozygous substitution of the C at position 526 by a T (526 C --> T), leading to an amino acid replacement of the FGF23 protein (R176W) at position 176. This causative new mutation is located in the consensus sequence for the proteolytic cleavage domain. These results confirm the importance of this site in FGF23 function and its essential role in ADHR physiopathology.
authors: Laboratoire de Cytogénétique, de Génétique Moléculaire et de Biologie de la Reproduction Humaines, Hôpital Farhat Hached, Rue Ibn El Jazzar, 4000 Sousse, Tunisia. moez.gribaa@rns.tn
authors: Moez
authors: M
authors: Gribaa
authors: Mohamed
authors: M
authors: Younes
authors: Yosra
authors: Y
authors: Bouyacoub
authors: Wided
authors: W
authors: Korbaa
authors: Ilhem
authors: I
authors: Ben Charfeddine
authors: Mongi
authors: M
authors: Touzi
authors: Labiba
authors: L
authors: Adala
authors: Ons
authors: O
authors: Mamay
authors: Naceur
authors: N
authors: Bergaoui
authors: Ali
authors: A
authors: Saad
mesh_terms: D003241:Consanguinity; D004252:DNA Mutational Analysis; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000235:genetics*; D005190:Family; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D014416:Tunisia
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23