Department of Developmental Genetics and Virology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Am J Hum Genet. 2010 Feb 12;86(2):273-8. doi: 10.1016/j.ajhg.2010.01.010. Epub 2010 Feb 4.
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.
已经证实，人类磷酸盐（Pi）处理和低血磷性佝偻病的紊乱是由 PHEX、FGF23 和 DMP1 的突变引起的，分别表现为 X 连锁隐性、常染色体显性和常染色体隐性遗传模式。我们通过定位克隆发现了一种外核苷酸焦磷酸酶/磷酸二酯酶 1（ENPP1）基因的失活突变，导致常染色体隐性低血磷性佝偻病（ARHR）伴磷酸尿。ENPP1 产生无机焦磷酸（PPi），这是一种重要的生理性钙化抑制剂，先前描述的该基因的失活突变导致异常的异位钙化紊乱，而我们的患者中没有异常的钙化。我们的意外结果表明，ARHR 的发生涉及不同的途径，并且 ENPP1 可能具有其他功能。
