{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:28:59Z","timestamp":1789216139358,"version":"build-2803163510"},"reference-count":42,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: Inactivating mutations of the calcium-sensing receptor (CASR) are implicated in different hypercalcemic syndromes, including familial hypocalciuric hypercalcemia (FHH), primary hyperparathyroidism (PHPT), and familial isolated hyperparathyroidism (FIHP). However, molecular diagnostics applied to large nonselected hypercalcemic cohorts from a single center have not been reported.<\/jats:p>\n               <jats:p>Objective: Our objective was to describe the prevalence, type, and potential pathogenicity of CASR mutations in a series of cases with FHH (n = 17), PHPT (n = 165), and FIHP (n = 3) and controls (n = 198) presenting at a single endocrine clinic.<\/jats:p>\n               <jats:p>Subjects: All were prospectively evaluated at the \u201cCasa Sollievo della Sofferenza\u201d Hospital in southern Italy over a 3-yr period.<\/jats:p>\n               <jats:p>Methods: CASR screening was conducted by denaturing HPLC. The variant CASRs were functionally characterized by transient transfection studies in kidney cells in vitro.<\/jats:p>\n               <jats:p>Results: A single novel missense variant was identified in one PHPT case. However, in FHH probands, mutations were found in eight of 17 (47%). With a hypercalcemic family member, mutation detection rate in FHH rose to seven of eight (87%), whereas only one of nine sporadic cases was positive, and none of the three FIHP cases had detectable CASR mutations. Five missense variant CASRs, identified in control subjects, performed as wild type in functional assays, whereas the missense mutant CASRs identified in the FHH patients, and in the one PHPT case, exhibited significant impairment. A novel intronic mutation (IVS4-19a\u2192c) found in one FHH family, created an abnormally spliced product in an in vitro minigene assay.<\/jats:p>\n               <jats:p>Conclusion: CASR testing, with functional analysis, provides critical confirmatory evidence in the differential diagnosis of hypercalcemic states.<\/jats:p>","DOI":"10.1210\/jc.2008-2430","type":"journal-article","created":{"date-parts":[[2010,2,18]],"date-time":"2010-02-18T02:34:35Z","timestamp":1266460475000},"page":"1819-1829","source":"Crossref","is-referenced-by-count":66,"title":["Calcium-Sensing Receptor (CASR) Mutations in Hypercalcemic States: Studies from a Single Endocrine Clinic Over Three Years"],"prefix":"10.1210","volume":"95","author":[{"given":"Vito","family":"Guarnieri","sequence":"first","affiliation":[{"name":"Genetics (V.G., L.A.M., A.N., L.D\u2019A.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Canaff","sequence":"first","affiliation":[{"name":"Departments of Medicine, Physiology, and Human Genetics (L.C., G.N.H.), McGill University; Calcium Research Laboratory, and Hormones and Cancer Research Unit, Royal Victoria Hospital, Montreal, Quebec, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco H. J.","family":"Yun","sequence":"first","affiliation":[{"name":"Departments of Laboratory Medicine and Pathobiology, Medicine, and Genetics (F.H.J.Y., B.Y.L.W., D.E.C.C.), University of Toronto, Ontario, Canada M5G 1L5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Scillitani","sequence":"first","affiliation":[{"name":"Endocrinology (A.S., C.B.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Battista","sequence":"first","affiliation":[{"name":"Endocrinology (A.S., C.B.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia A.","family":"Muscarella","sequence":"first","affiliation":[{"name":"Genetics (V.G., L.A.M., A.N., L.D\u2019A.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty Y. L.","family":"Wong","sequence":"first","affiliation":[{"name":"Departments of Laboratory Medicine and Pathobiology, Medicine, and Genetics (F.H.J.Y., B.Y.L.W., D.E.C.C.), University of Toronto, Ontario, Canada M5G 1L5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelantonio","family":"Notarangelo","sequence":"first","affiliation":[{"name":"Genetics (V.G., L.A.M., A.N., L.D\u2019A.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"D'Agruma","sequence":"first","affiliation":[{"name":"Genetics (V.G., L.A.M., A.N., L.D\u2019A.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Sacco","sequence":"first","affiliation":[{"name":"Pediatrics (M.S.), Units, Hospital Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carrattere Scientifico, 71013 San Giovanni Rotondo (Foggia), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E. 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