X-linked hypophosphataemia: a homologous disorder in humans and mice

被引:124
作者
Tenenhouse, HS
机构
[1] McGill Univ, Montreal Childrens Hosp, Res Inst, Dept Pediat, Montreal, PQ H3H 1P3, Canada
[2] McGill Univ, Montreal Childrens Hosp, Res Inst, Dept Human Genet, Montreal, PQ H3H 1P3, Canada
关键词
Hyp; Gy; PHEX; Phex; phosphate transport; vitamin D; kidney; bone; endopeptidase;
D O I
10.1093/ndt/14.2.333
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
X-linked hypophosphatemia is an inherited disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets and osteomalacia, hypophosphataemia, and aberrant renal Pi reabsorption and vitamin D metabolism. Studies in murine Hyp and Gy homologues have identified a specific defect in Na+-Pi cotransport at the brush border membrane, abnormal regulation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D) synthesis and degradation, and an intrinsic defect in bone mineralization. The mutant gene has been identified in XLH patients, by positional cloning, and in Hyp and Gy mice, and was designated PHEX/Phex to signify a PHosphate-regulating gene with homology to Endopeptidases on the X chromosome. PHEX/Phex is expressed in bones and teeth but not in kidney and efforts are under way to elucidate how loss of PHEX/Phex function elicits the mutant phenotype. Based on its homology to endopeptidases, it is postulated that PHEX/Phex is involved in the activation or inactivation of a peptide hormone(s) which plays a key role in the regulation of bone mineralization, renal Pi handling and vitamin D metabolism.
引用
收藏
页码:333 / 341
页数:9
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