{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:23Z","timestamp":1784557043872,"version":"3.55.0"},"reference-count":20,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"Summary<\/jats:title>\n \n A\n de novo<\/jats:italic>\n heterozygous inactivating mutation of calcium-sensing receptor (\n CASR<\/jats:italic>\n ) gene typically causes neonatal hyperparathyroidism (NHPT) with moderate hypercalcemia and hyperparathyroid bone disease. We present a case of asymptomatic hypocalciuric hypercalcemia with a\n de novo<\/jats:italic>\n heterozygous mutation in\n CASR<\/jats:italic>\n , S591C, which is primarily reported to be responsible for NHPT. A 54-year-old female was referred for investigation of asymptomatic hypercalcemia that was initially found in the 1980s but without a history of bone disease during the perinatal period. She had moderate hypercalcemia (12.4\u200amg\/dl) and relative hypocalciuria (fractional extraction of calcium 1.07%) but normal intact parathyroid hormone and serum 1,25-dihydroxyvitamin D\n 3<\/jats:sub>\n . Pedigree analysis revealed that she carried a\n de novo<\/jats:italic>\n heterozygous mutation of S591C, which she transmitted to an affected child with moderate hypercalcemia but not to other children, who had normal serum calcium levels. A\n de novo<\/jats:italic>\n heterozygous\n CASR<\/jats:italic>\n mutation that is responsible for NHPT may also present in individuals with asymptomatic hypocalciuric hypercalcemia. Caution is required when predicting course and outcome in a pedigree with\n CASR<\/jats:italic>\n mutation, as well as incidental hypercalcemia, because of its variable phenotypes.\n <\/jats:p>\n \n Learning points<\/jats:title>\n \n \n \n \n The phenotype and severity of\n CASR<\/jats:italic>\n mutations are thought to be dependent on genotypes.\n <\/jats:p>\n <\/jats:list-item>\n \n \n We report an asymptomatic case of the\n de novo<\/jats:italic>\n heterozygous S591C mutation in\n CASR<\/jats:italic>\n , which has previously been reported as a responsible mutation of NHPT with bone diseases.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Variable phenotypes of\n CASR<\/jats:italic>\n raise a cautionary note about predicting outcome by genotyping in a pedigree with\n CASR<\/jats:italic>\n mutation.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/edm-15-0016","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T04:24:26Z","timestamp":1432182266000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":8,"title":["Familial hypocalciuric hypercalcemia with a de novo heterozygous mutation of calcium-sensing receptor"],"prefix":"10.1530","volume":"2015","author":[{"given":"Katsumi","family":"Taki","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Fujiyoshida Municipal Medical Center, Yamanashi, 403-0005, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Kogai","sequence":"additional","affiliation":[{"name":"1 Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Sakumoto","sequence":"additional","affiliation":[{"name":"1 Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Namatame","sequence":"additional","affiliation":[{"name":"2 Clinical Research Center, Dokkyo Medical University, Tochigi, 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hishinuma","sequence":"additional","affiliation":[{"name":"1 Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, 321-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref01","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1046\/j.1365-2265.1999.00788.x","article-title":"Casting new light on the clinical spectrum of 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