{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:26:23Z","timestamp":1790753183950,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2020,6]]},"DOI":"10.1016\/j.ajhg.2020.04.006","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T10:37:07Z","timestamp":1588847827000},"page":"734-747","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":83,"title":["Familial Hypocalciuric Hypercalcemia Type 1 and Autosomal-Dominant Hypocalcemia Type 1: Prevalence in a Large Healthcare Population"],"prefix":"10.1016","volume":"106","author":[{"given":"Ridge","family":"Dershem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Gorvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghu P.R.","family":"Metpally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarathbabu","family":"Krishnamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane T.","family":"Smelser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadil M.","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh V.","family":"Thakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-0362","authenticated-orcid":false,"given":"Gerda E.","family":"Breitwieser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2020.04.006_bib1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.beem.2013.02.006","article-title":"Role of the calcium-sensing receptor in extracellular calcium homeostasis","volume":"27","author":"Brown","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib2","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/dds105","article-title":"Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites","volume":"21","author":"Hannan","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2020.04.006_bib3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.beem.2013.05.010","article-title":"Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways","volume":"27","author":"Conigrave","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib4","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.celrep.2017.12.089","article-title":"AP2\u03c3 mutations impair calcium-sensing receptor trafficking and signaling, and show an endosomal pathway to spatially direct G-protein selectivity","volume":"22","author":"Gorvin","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.ajhg.2020.04.006_bib5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.beem.2013.04.007","article-title":"Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism","volume":"27","author":"Hannan","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib6","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1210\/jc.2014-1414","article-title":"Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop","volume":"99","author":"Eastell","year":"2014","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib7","doi-asserted-by":"crossref","DOI":"10.4158\/EP-2018-0350","article-title":"Calcium creatinine ratio is not helpful in differentiation primary hyperparathyroidism from familial hypercalcemic hypocalciuria: A study of 1000 patients","author":"Moore","year":"2018","journal-title":"Endocr. Pract."},{"key":"10.1016\/j.ajhg.2020.04.006_bib8","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1530\/JME-16-0124","article-title":"Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis","volume":"57","author":"Hannan","year":"2016","journal-title":"J.\u00a0Mol. Endocrinol."},{"key":"10.1016\/j.ajhg.2020.04.006_bib9","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1056\/NEJMoa1300253","article-title":"Mutations affecting G-protein subunit \u03b111 in hypercalcemia and hypocalcemia","volume":"368","author":"Nesbit","year":"2013","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2020.04.006_bib10","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12020-017-1241-5","article-title":"Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia","volume":"55","author":"Szalat","year":"2017","journal-title":"Endocrine"},{"key":"10.1016\/j.ajhg.2020.04.006_bib11","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1530\/EJE-16-0842","article-title":"AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia","volume":"176","author":"Hovden","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.ajhg.2020.04.006_bib12","doi-asserted-by":"crossref","first-page":"E1311","DOI":"10.1210\/jc.2014-1120","article-title":"Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations","volume":"99","author":"Hendy","year":"2014","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib13","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s002230001201","article-title":"The prevalence of familial hypocalciuric hypercalcemia","volume":"68","author":"Hinnie","year":"2001","journal-title":"Calcif. Tissue Int."},{"key":"10.1016\/j.ajhg.2020.04.006_bib14","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1210\/jc.2012-4022","article-title":"Incidence and prevalence of primary hyperparathyroidism in a racially mixed population","volume":"98","author":"Yeh","year":"2013","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib15","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/gim.2015.187","article-title":"The Geisinger MyCode community health initiative: an electronic health record-linked biobank for precision medicine research","volume":"18","author":"Carey","year":"2016","journal-title":"Genet. Med."},{"key":"10.1016\/j.ajhg.2020.04.006_bib16","doi-asserted-by":"crossref","first-page":"6319","DOI":"10.1126\/science.aaf6814","article-title":"Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study","volume":"354","author":"Dewey","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2020.04.006_bib17","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.ajhg.2018.03.012","article-title":"Profiling and leveraging relatedness in a Precision Medicine Cohort of 92,455 exomes","volume":"102","author":"Staples","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2020.04.006_bib18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12859-018-2591-6","article-title":"Real world scenarios in rare variant association analysis: the impact of imbalance and sample size on the power in\u00a0silico","volume":"20","author":"Zhang","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.ajhg.2020.04.006_bib19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"10.1016\/j.ajhg.2020.04.006_bib20","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1159\/000320560","article-title":"Calcium sensing receptor mutations implicated in pancreatitis and idiopathic epilepsy syndrome disrupt an arginine-rich retention motif","volume":"26","author":"Stepanchick","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"10.1016\/j.ajhg.2020.04.006_bib21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jbmr.3241","article-title":"Cinacalcet rectifies hypercalcemia in a patient with familial hypocalciuric hypercalcemia type 2 (FHH2) caused by a germline loss-of-function Galpha11 mutation","volume":"33","author":"Gorvin","year":"2018","journal-title":"J.\u00a0Bone Miner. Res."},{"key":"10.1016\/j.ajhg.2020.04.006_bib22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1126\/scisignal.aan3714","article-title":"A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate \u03b2-arrestin-biased signaling","volume":"11","author":"Gorvin","year":"2018","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ajhg.2020.04.006_bib23","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1002\/jbmr.483","article-title":"Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research","volume":"26","author":"Bilezikian","year":"2011","journal-title":"J.\u00a0Bone Miner. Res."},{"key":"10.1016\/j.ajhg.2020.04.006_bib24","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cca.2011.12.004","article-title":"Identification of rare and frequent variants of the CASR gene by high-resolution melting","volume":"413","author":"Nissen","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.ajhg.2020.04.006_bib25","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1046\/j.1365-2265.2000.01042.x","article-title":"A new missense mutation in the calcium-sensing receptor in familial benign hypercalcaemia associated with partial lipoatrophy and insulin resistant diabetes","volume":"53","author":"Vigouroux","year":"2000","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"10.1016\/j.ajhg.2020.04.006_bib26","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1172\/JCI118987","article-title":"Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells","volume":"98","author":"Pearce","year":"1996","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ajhg.2020.04.006_bib27","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/cen.14078","article-title":"Expanding the spectrum of genetic variants in the calcium-sensing receptor (CASR) gene in hypercalcemic individuals","volume":"91","author":"Nissen","year":"2019","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"10.1016\/j.ajhg.2020.04.006_bib28","doi-asserted-by":"crossref","first-page":"L29","DOI":"10.1210\/jc.2014-4221","article-title":"Letter to the editor: Distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium","volume":"100","author":"Marx","year":"2015","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib29","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1210\/jc.2008-2430","article-title":"Calcium-sensing receptor (CASR) mutations in hypercalcemic states: studies from a single endocrine clinic over three years","volume":"95","author":"Guarnieri","year":"2010","journal-title":"J.\u00a0Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ajhg.2020.04.006_bib30","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/0002-9343(77)90873-7","article-title":"Family studies in patients with primary parathyroid hyperplasia","volume":"62","author":"Marx","year":"1977","journal-title":"Am. J. Med."},{"key":"10.1016\/j.ajhg.2020.04.006_bib31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12859-018-2135-0","article-title":"A simulation study investigating power estimates in phenome-wide association studies","volume":"19","author":"Verma","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.ajhg.2020.04.006_bib32","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1530\/EJE-16-1037","article-title":"Associations between serum levels of calcium, parathyroid hormone and future risk of venous thromboembolism: the Troms\u00f8 study","volume":"176","author":"Lerstad","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.ajhg.2020.04.006_bib33","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jjcc.2013.08.003","article-title":"Hypocalcemia is related to left ventricular diastolic dysfunction in patients with chronic kidney disease","volume":"63","author":"Gromadzi\u0144ski","year":"2014","journal-title":"J.\u00a0Cardiol."},{"key":"10.1016\/j.ajhg.2020.04.006_bib34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.psychres.2017.01.101","article-title":"Relationship between serum calcium and neuropsychological performance might indicate etiological heterogeneity underlying cognitive deficits in schizophrenia and depression","volume":"252","author":"Sharma","year":"2017","journal-title":"Psychiatry Res."},{"key":"10.1016\/j.ajhg.2020.04.006_bib35","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.psyneuen.2018.03.012","article-title":"Serum calcium levels and neuropsychological performance in depression and matched healthy controls: Reversal of correlation a marker of the aging cognitive clock?","volume":"91","author":"Gr\u00fctzner","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.ajhg.2020.04.006_bib36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1530\/EJE-16-0369","article-title":"The cardiovascular system in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene","volume":"175","author":"Breum Jakobsen","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.ajhg.2020.04.006_bib37","first-page":"30323","article-title":"Calcium sensing receptor expression and signalling in cardiovascular physiology and disease","volume":"1891","author":"Schreckenberg","year":"2018","journal-title":"Vascul. Pharmacol."},{"key":"10.1016\/j.ajhg.2020.04.006_bib38","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.3390\/molecules24142546","article-title":"The nervous system relevance of the calcium sensing receptor in health and disease","volume":"24","author":"Giudice","year":"2019","journal-title":"Molecules"}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929720301154?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929720301154?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:18:58Z","timestamp":1757575138000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929720301154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["S0002929720301154"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2020.04.006","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Familial Hypocalciuric Hypercalcemia Type 1 and Autosomal-Dominant Hypocalcemia Type 1: Prevalence in a Large Healthcare Population","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2020.04.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors.","name":"copyright","label":"Copyright"}]}}