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标题：A translocation causing increased α-Klotho level results in hypophosphatemic rickets and hyperparathyroidism
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作者：Catherine A. Brownstein ; Felix Adler ; Carol Nelson-Williams 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：9
页码：3455-3460
DOI：10.1073/pnas.0712361105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Phosphate homeostasis is central to diverse physiologic processes including energy homeostasis, formation of lipid bilayers, and bone formation. Reduced phosphate levels due to excessive renal loss cause hypophosphatemic rickets, a disease characterized by prominent bone defects; conversely, hyperphosphatemia, a major complication of renal failure, is accompanied by parathyroid hyperplasia, hyperparathyroidism, and osteodystrophy. Here, we define a syndrome featuring both hypophosphatemic rickets and hyperparathyroidism due to parathyroid hyperplasia as well as other skeletal abnormalities. We show that this disease is due to a de novo translocation with a breakpoint adjacent to {alpha}-Klotho, which encodes a {beta}-glucuronidase, and is implicated in aging and regulation of FGF signaling. Plasma {alpha}-Klotho levels and {beta}-glucuronidase activity are markedly increased in the affected patient; unexpectedly, the circulating FGF23 level is also markedly elevated. These findings suggest that the elevated {alpha}-Klotho level mimics aspects of the normal response to hyperphosphatemia and implicate {alpha}-Klotho in the selective regulation of phosphate levels and in the regulation of parathyroid mass and function; they also have implications for the pathogenesis and treatment of renal osteodystrophy in patients with kidney failure.
关键词：bone ; endocrinology ; genetics ; phosphorus