Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification

J Bone Miner Res. 2013 Jun;28(6):1378-85. doi: 10.1002/jbmr.1850.

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.

Publication types

  • Case Reports
  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Calcinosis* / genetics
  • Calcinosis* / metabolism
  • Calcinosis* / pathology
  • Casein Kinase I
  • DNA Mutational Analysis
  • Exome*
  • Extracellular Matrix Proteins* / genetics
  • Extracellular Matrix Proteins* / metabolism
  • Female
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Hypophosphatemia, Familial* / genetics
  • Hypophosphatemia, Familial* / metabolism
  • Hypophosphatemia, Familial* / pathology
  • Male
  • Mutation
  • Norway
  • Osteosclerosis / genetics
  • Osteosclerosis / metabolism
  • Osteosclerosis / pathology
  • Tooth Abnormalities* / genetics
  • Tooth Abnormalities* / metabolism
  • Tooth Abnormalities* / pathology

Substances

  • Extracellular Matrix Proteins
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Casein Kinase I
  • FAM20C protein, human