title: Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification.
abstract: Fibroblast growth factor 23 (FGF23) plays a crucial role in renal phosphate regulation, exemplified by the causal role of PHEX and DMP1 mutations in X-linked hypophosphatemic rickets and autosomal recessive rickets type 1, respectively. Using whole exome sequencing we identified compound heterozygous mutations in family with sequence similarity 20, member C (FAM20C) in two siblings referred for hypophosphatemia and severe dental demineralization disease. FAM20C mutations were not found in other undiagnosed probands of a national Norwegian population of familial hypophosphatemia. Our results demonstrate that mutations in FAM20C provide a putative new mechanism in human subjects leading to dysregulated FGF23 levels, hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis of the long bones in the absence of rickets.
authors: Department of Clinical Medicine, University of Bergen, Bergen, Norway. silje.rafaelsen@pedi.uib.no
authors: Silje Hjorth
authors: SH
authors: Rafaelsen
authors: Helge
authors: H
authors: Raeder
authors: Anne Kristine
authors: AK
authors: Fagerheim
authors: Per
authors: P
authors: Knappskog
authors: Thomas O
authors: TO
authors: Carpenter
authors: Stefan
authors: S
authors: Johansson
authors: Robert
authors: R
authors: Bjerknes
mesh_terms: D000293:Adolescent; D000328:Adult; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047389:Casein Kinase I; D004252:DNA Mutational Analysis; D059472:Exome; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D009664:Norway; D010026:Osteosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014071:Tooth Abnormalities / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D047389:Casein Kinase I; C524449:FAM20C protein, human