Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene

Varda Levy-Litan, Eli Hershkovitz, Luba Avizov, Neta Leventhal, Dani Bercovich, Vered Chalifa-Caspi, Esther Manor, Sophia Buriakovsky, Yair Hadad, James Goding, Ruti Parvari

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

Abstract

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalAmerican Journal of Human Genetics
Volume86
Issue number2
DOIs
StatePublished - 12 Feb 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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