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Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene |
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| Authors: | Varda Levy-Litan Eli Hershkovitz Luba Avizov Dani Bercovich Esther Manor Sophia Buriakovsky James Goding |
| Affiliation: | 1 Department of Developmental Genetics and Virology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel 2 Pediatric Endocrinology & Metabolim Unit, Soroka Medical Center, Beer Sheva 84101 and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel 3 Migal- Galilee Technology Center & Tel Hai Academic College, Kiryat-Shmona 11016, Israel 4 National Institute of Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva 84105, Israel 5 Institute of Genetics, Soroka Medical Center, Beer Sheva 84105, Israel 6 Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel 7 Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University, Rehovot 76100, Israel 8 Department of Physiology, Monash University, Victoria 3800, Australia |
| 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. |
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