Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23

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

Research output: Contribution to journalArticle

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Abstract

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
Pages (from-to)345-348
Number of pages4
JournalNature Genetics
Volume26
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Mutation
Phosphates
Fibroblast Growth Factors
Genes
Familial Hypophosphatemic Rickets
Molecular Sequence Annotation
Bone and Bones
Neprilysin
Osteomalacia
Rickets
Missense Mutation
Serum
Phosphorus
Organism Cloning
Lower Extremity
Tooth
Homeostasis
Autosomal Dominant Hypophosphatemic Rickets
Pain
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

White, K., Evans, W. E., O'Riordan, J. L. H., Speer, M. C., Econs, M., Lorenz-Depiereux, B., ... Strom, T. M. (2000). Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nature Genetics, 26(3), 345-348. https://doi.org/10.1038/81664

Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. / White, Kenneth; Evans, Wayne E.; O'Riordan, Jeffery L H; Speer, Marcy C.; Econs, Michael; Lorenz-Depiereux, Bettina; Grabowski, Monika; Meitinger, Thomas; Strom, Tim M.

In: Nature Genetics, Vol. 26, No. 3, 2000, p. 345-348.

Research output: Contribution to journalArticle

White, K, Evans, WE, O'Riordan, JLH, Speer, MC, Econs, M, Lorenz-Depiereux, B, Grabowski, M, Meitinger, T & Strom, TM 2000, 'Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23', Nature Genetics, vol. 26, no. 3, pp. 345-348. https://doi.org/10.1038/81664
White, Kenneth ; Evans, Wayne E. ; O'Riordan, Jeffery L H ; Speer, Marcy C. ; Econs, Michael ; Lorenz-Depiereux, Bettina ; Grabowski, Monika ; Meitinger, Thomas ; Strom, Tim M. / Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. In: Nature Genetics. 2000 ; Vol. 26, No. 3. pp. 345-348.
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