Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23

Kenneth E. White, Wayne E. Evans, Jeffery L.H. O'Riordan, Marcy C. Speer, Michael J. Econs, Bettina Lorenz-Depiereux, Monika Grabowski, Thomas Meitinger, Tim M. Strom

Research output: Contribution to journalArticlepeer-review

1099 Scopus citations


Proper serum phosphate concentrations are maintained by a complex and poorly understood process. Identification of genes responsible for inherited disorders involving disturbances in phosphate homeostasis may provide insight into the pathways that regulate phosphate balance. Several hereditary disorders of isolated phosphate wasting have been described, including X-linked hypophosphataemic rickets1 (XLH), hypophosphataemic bone disease2 (HBD), hereditary hypophosphataemic rickets with hypercalciuria3 (HHRH) and autosomal dominant hypophosphataemic rickets4,5 (ADHR). Inactivating mutations of the gene PHEX, encoding a member of the neutral endopeptidase family of proteins, are responsible for XLH (refs 6,7). ADHR (MIM 193100) is characterized by low serum phosphorus concentrations, rickets, osteomalacia, lower extremity deformities, short stature, bone pain and dental abscesses4,5. Here we describe a positional cloning approach used to identify the ADHR gene which included the annotation of 37 genes within 4 Mb of genomic sequence. We identified missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23. These mutations in patients with ADHR represent the first mutations found in a human FGF gene.

Original languageEnglish (US)
Pages (from-to)345-348
Number of pages4
JournalNature genetics
Issue number3
StatePublished - Nov 20 2000

ASJC Scopus subject areas

  • Genetics

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