Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets

J Hum Genet. 2012 Jul;57(7):453-8. doi: 10.1038/jhg.2012.56. Epub 2012 Jun 14.


This study aimed to identify the underlying genetic mutation in patients with hypophosphatemic rickets (HR). Genomic DNA was analysed for mutations in PHEX, FGF23 and CLCN5 by polymerase chain reaction (PCR) followed by denaturing high-performance liquid chromatography (dHPLC). Bi-directional sequencing was performed in samples with deviating chromatographic profiles. DMP1 and SLC34A3 were sequenced, only. In addition, a multiplex ligation-dependent probe amplification (MLPA) analysis was performed to detect larger deletions/duplications in PHEX or FGF23. Familial cases accounted for 12 probands while 12 cases were sporadic. In 20 probands, mutations were detected in PHEX of which 12 were novel, and one novel frameshift mutation was found in DMP1. Three PHEX mutations were identified by the MLPA analysis only; that is, two large deletions and one duplication. No mutations were identified in FGF23, SLC34A3 or CLCN5. By the methods used, a disease causing mutation was identified in 83% of the familial and 92% of the sporadic cases, thereby in 88% of the tested probands. Genetic analysis performed in HR patients by PCR, dHPLC, sequencing and in addition by MLPA analysis revealed a high identification rate of gene mutations causing HR, including 12 novel PHEX and one novel DMP1 mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Child
  • Child, Preschool
  • Chloride Channels / genetics
  • Chromatography, High Pressure Liquid / methods
  • Codon, Nonsense / genetics
  • Cross-Sectional Studies
  • DNA Mutational Analysis / methods*
  • Extracellular Matrix Proteins / genetics*
  • Familial Hypophosphatemic Rickets / genetics*
  • Female
  • Fibroblast Growth Factors / genetics
  • Frameshift Mutation
  • Genetic Testing / methods
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Mutation, Missense
  • PHEX Phosphate Regulating Neutral Endopeptidase / genetics*
  • Pedigree
  • Phosphoproteins / genetics*
  • Polymerase Chain Reaction
  • Sodium-Phosphate Cotransporter Proteins, Type IIc / genetics


  • CLC-5 chloride channel
  • Chloride Channels
  • Codon, Nonsense
  • DMP1 protein, human
  • Extracellular Matrix Proteins
  • Phosphoproteins
  • SLC34A3 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type IIc
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • PHEX protein, human