{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:01:17Z","timestamp":1753891277534,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In recent years, heterozygous loss-of-function mutations of the Calcium Sensing Receptor gene (CaSR) were implicated in different hypercalcemic syndromes besides familial hypocalciuric hypercalcemia (FHH), including neonatal severe primary hyperparathyroidism (NSHPT) and primary hyperparathyroidism (PHPT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Cases presentation<\/jats:title><jats:p>Here we describe two unusual presentations of heterozygous inactivating CaSR mutations. Case 1: a case of NSHPT due to a <jats:italic>de novo<\/jats:italic>, p.(ArgR185Gln) CaSR mutation and successfully treated with cinacalcet monotherapy for 8 years until definitive surgical resolution. Case 2: a 37 years-old woman with PHPT complicated with hypercalcemia and nephrocalcinosis with a novel heterozygous p.(Pro393Arg) CaSR mutation and cured with parathyroidectomy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These cases reinforce the fact that the clinical spectrum of inactivating mutations of the CaSR has widened and, although carrying a mutation suggestive of FHH, some patients may have different clinical phenotypes and complications requiring individualized therapies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2021.809067","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T04:39:55Z","timestamp":1642999195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Unusual Presentations of Loss-of-Function Mutations of the Calcium-Sensing Receptor"],"prefix":"10.3389","volume":"8","author":[{"given":"Serena","family":"Palmieri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Grassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito","family":"Guarnieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iacopo","family":"Chiodini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Arosio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Eller-Vainicher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.berh.2007.11.006","article-title":"Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations","volume":"22","author":"Egbuna","year":"2008","journal-title":"Best Pract Res Clin Rheumatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1159\/000491038","article-title":"Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism","volume":"51","author":"Vannucci","year":"2019","journal-title":"Front Horm Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"60","DOI":"10.11138\/ccmbm\/2017.14.1.060","article-title":"Molecular genetics in primary hyperparathyroidism: the role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning. 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