{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:06:03Z","timestamp":1791417963502,"version":"4.3.3"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,3,4]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>de novo<\/jats:italic>\n                    translocation with a breakpoint adjacent to \u03b1-\n                    <jats:italic>Klotho<\/jats:italic>\n                    , which encodes a \u03b2-glucuronidase, and is implicated in aging and regulation of FGF signaling. Plasma \u03b1-Klotho levels and \u03b2-glucuronidase activity are markedly increased in the affected patient; unexpectedly, the circulating FGF23 level is also markedly elevated. These findings suggest that the elevated \u03b1-Klotho level mimics aspects of the normal response to hyperphosphatemia and implicate \u03b1-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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0712361105","type":"journal-article","created":{"date-parts":[[2008,2,28]],"date-time":"2008-02-28T21:11:37Z","timestamp":1204233097000},"page":"3455-3460","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":211,"title":["A translocation causing increased \u03b1-Klotho level results in hypophosphatemic rickets and hyperparathyroidism"],"prefix":"10.1073","volume":"105","author":[{"given":"Catherine A.","family":"Brownstein","sequence":"first","affiliation":[{"name":"*Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Adler","sequence":"additional","affiliation":[{"name":"*Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Nelson-Williams","sequence":"additional","affiliation":[{"name":"*Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;"},{"name":"Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peining","family":"Li","sequence":"additional","affiliation":[{"name":"*Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Imura","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;"},{"name":"Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yo-ichi","family":"Nabeshima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;"},{"name":"Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan; 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