{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:26:07Z","timestamp":1787163967625,"version":"build-2736575974"},"reference-count":13,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We report a patient who initially presented at 4 days old with hypocalcemia, hypoparathyroidism, and elevated phosphorous level. Treatment was initiated with calcitriol, calcium carbonate (CaCO3), vitamin D, and low phosphorous formula. Family history was positive for an activating calcium sensing receptor (CASR) variant (R990G) identified previously in 2 older siblings who were treated with CaCO3 and calcitriol. However, genetic studies were negative for the CASR variant in our patient. She maintained a large calcium requirement and was admitted for multiple episodes of hypocalcemia. Further investigation revealed that the CASR variant identified in the older siblings was now considered a benign, nondisease-causing variant. Whole exome sequencing on our proband revealed a homozygous pathogenic variant in the GCM2 gene (Gln392*) consistent with a molecular diagnosis of familial isolated hypoparathyroidism. Genetic studies revealed the 2 older siblings harbor the same genetic changes and parents are heterozygous carriers for this allele. Due to persistent hypocalcemia, we initiated teriparatide. She weaned off calcitriol and achieved normocalcemia on teriparatide, CaCO3, and vitamin D. Siblings transitioned to the same treatment without complications. These findings demonstrate the importance of adequate diagnostic genetic testing and the role of variant reanalysis over time in promoting accurate diagnoses.<\/jats:p>","DOI":"10.1210\/jcemcr\/luae185","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T23:21:11Z","timestamp":1728343271000},"source":"Crossref","is-referenced-by-count":3,"title":["Three Siblings With Familial Isolated Hypoparathyroidism: A Diagnostic Journey From\n                    <i>CASR<\/i>\n                    to Novel\n                    <i>GCM2<\/i>\n                    Variant"],"prefix":"10.1210","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8535-1413","authenticated-orcid":false,"given":"Apisadaporn","family":"Thambundit","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology, UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian A","family":"Martinez-Agosto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics , UCLA, Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Kianmahd Shamshoni","sequence":"additional","affiliation":[{"name":"Department of Human Genetics , UCLA, Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen K","family":"Winer","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D","family":"Mittelman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"2024110705245170900_luae185-B1","doi-asserted-by":"crossref","first-page":"17055","DOI":"10.1038\/nrdp.2017.55","article-title":"Hypoparathyroidism","volume":"3","author":"Mannstadt","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"8","key":"2024110705245170900_luae185-B2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1530\/EC-17-0234","article-title":"Impact of intercurrent illness on calcium homeostasis in children with hypoparathyroidism: a case series","volume":"6","author":"Chinoy","year":"2017","journal-title":"Endocr Connect"},{"issue":"15","key":"2024110705245170900_luae185-B3","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1056\/NEJM199610103351505","article-title":"A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor","volume":"335","author":"Pearce","year":"1996","journal-title":"N Engl J Med"},{"key":"2024110705245170900_luae185-B4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000491043","article-title":"Classification of hypoparathyroid disorders","volume":"51","author":"Cianferotti","year":"2019","journal-title":"Front Horm Res"},{"issue":"4","key":"2024110705245170900_luae185-B5","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.ecl.2018.07.007","article-title":"Genetic disorders of parathyroid development and function","volume":"47","author":"Gordon","year":"2018","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"11","key":"2024110705245170900_luae185-B6","doi-asserted-by":"crossref","first-page":"E2421","DOI":"10.1210\/jc.2014-2174","article-title":"Comprehensive next-generation sequencing analyses of hypoparathyroidism: identification of novel GCM2 mutations","volume":"99","author":"Mitsui","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"6792","key":"2024110705245170900_luae185-B7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/35018111","article-title":"Genetic ablation of parathyroid glands reveals another source of parathyroid hormone","volume":"406","author":"G\u00fcnther","year":"2000","journal-title":"Nature"},{"issue":"7-8","key":"2024110705245170900_luae185-B8","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1515\/jpem-2012-0080","article-title":"A novel mutation in the GCM2 gene causing severe congenital isolated hypoparathyroidism","volume":"25","author":"Doyle","year":"2012","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"4","key":"2024110705245170900_luae185-B9","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1210\/jc.2007-1783","article-title":"Analysis of the GCM2 gene in isolated hypoparathyroidism: a molecular and biochemical study","volume":"93","author":"Maret","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2024110705245170900_luae185-B10","doi-asserted-by":"crossref","first-page":"115977","DOI":"10.1016\/j.bone.2021.115977","article-title":"Therapy with PTH 1-34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center","volume":"149","author":"Winer","year":"2021","journal-title":"Bone"},{"issue":"16","key":"2024110705245170900_luae185-B11","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1056\/NEJMc063043","article-title":"Recombinant PTH for initial management of neonatal hypocalcemia","volume":"356","author":"Newfield","year":"2007","journal-title":"N Engl J Med"},{"issue":"7","key":"2024110705245170900_luae185-B12","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1210\/jc.2005-2605","article-title":"A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone","volume":"91","author":"Mittelman","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2024110705245170900_luae185-B13","doi-asserted-by":"crossref","first-page":"msae015","DOI":"10.1093\/molbev\/msae015","article-title":"Exploring adaptive phenotypes for the human calcium-sensing receptor polymorphism R990G","volume":"41","author":"Sinigaglia","year":"2024","journal-title":"Mol Biol Evol"}],"container-title":["JCEM Case 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