{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:17:41Z","timestamp":1757704661659,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominantly inherited disorder with overlapping biochemistry profile with primary hyperparathyroidism (PHPT), making the correct diagnosis a challenge. The objective of the study was to evaluate the results of the clinical work\u2010up of a large group of hypercalcemic individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Cross\u2010sectional study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Patients undergoing clinical work\u2010up of hypercalcemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Molecular genetic analysis of the <jats:italic>CASR<\/jats:italic> gene and exon 2 of the <jats:italic>AP2S1<\/jats:italic> gene. Plasma levels of ionized calcium and PTH as well as calcium creatinine clearance ratio (CCCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A rare <jats:italic>CASR<\/jats:italic> variant was identified in 38 of 624 index patients (6.1%). A total of 18 <jats:italic>CASR<\/jats:italic> variants identified in this study were novel. No variants were identified in exon 2 of the <jats:italic>AP2S1<\/jats:italic> gene. The majority of the variants (N\u00a0=\u00a016) were classified as likely pathogenic. The level of plasma calcium, plasma PTH and the CCCR was not affected by the type of variant (ie nonsense vs missense) (all <jats:italic>P<\/jats:italic>\u2010values &gt;.05). The CCCR was found to be significantly lower for variants in the transmembrane domain compared with variants located in the extracellular domain (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Plasma levels of calcium and PTH were not associated with the location of the variant (<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We expanded the spectrum of <jats:italic>CASR<\/jats:italic> variants in hypercalcemia with 18 novel variants, and suggest that the location of the <jats:italic>CASR<\/jats:italic> variant may affect calcium excretion as determined by the CCCR.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14078","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T17:33:13Z","timestamp":1566408793000},"page":"683-690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expanding the spectrum of genetic variants in the calcium\u2010sensing receptor (<i>CASR<\/i>) gene in hypercalcemic individuals"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8201-1306","authenticated-orcid":false,"given":"Peter H.","family":"Nissen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Rejnmark","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital Aarhus 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