{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:26:09Z","timestamp":1775737569161,"version":"3.50.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,9]]},"abstract":"\nObjective<\/jats:title>\nAutosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and inappropriately low PTH concentrations. ADH type 1 is caused by activating mutations in the calcium-sensing receptor (CASR), a G-protein-coupled receptor signaling through \u03b111<\/jats:sub> (G\u03b111<\/jats:sub>) and \u03b1q<\/jats:sub> (G\u03b1q<\/jats:sub>) subunits. Heterozygous activating mutations in GNA11<\/jats:italic>, the gene encoding G\u03b111<\/jats:sub>, underlie ADH type 2. This study describes disease characteristics in a family with ADH caused by a gain-of-function mutation in GNA11<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n\nDesign<\/jats:title>\nA three-generation family with seven members (3 adults, 4 children) presenting with ADH.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nBiochemical parameters of calcium metabolism, clinical, genetic and brain imaging findings were analyzed.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nSanger sequencing revealed a heterozygous GNA11<\/jats:italic> missense mutation (c.1018G>A, p.V340M) in all seven hypocalcemic subjects, but not in the healthy family members (n<\/jats:italic>=4). The adult patients showed clinical symptoms of hypocalcemia, while the children were asymptomatic. Plasma ionized calcium ranged from 0.95 to 1.14mmol\/L, yet plasma PTH was inappropriately low for the degree of hypocalcemia. Serum 25OHD was normal. Despite hypocalcemia 1,25(OH)2<\/jats:sub>D and urinary calcium excretion were inappropriately in the reference range. None of the patients had nephrocalcinosis. Two adults and one child (of the two MRI scanned children) had distinct intracranial calcifications. All affected subjects had short stature (height s.d.<\/jats:sc> scores ranging from \u22123.4 to \u22122.3 vs \u22120.5 in the unaffected children).<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nThe identified GNA11<\/jats:italic> mutation results in biochemical abnormalities typical for ADH. Additional features, including short stature and early intracranial calcifications, cosegregated with the mutation. These findings may indicate a wider role for G\u03b111<\/jats:sub> signaling besides calcium regulation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0109","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T02:53:50Z","timestamp":1466650430000},"page":"211-218","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":30,"title":["Impaired growth and intracranial calcifications in autosomal dominant hypocalcemia caused by a GNA11 mutation"],"prefix":"10.1093","volume":"175","author":[{"given":"Sirpa","family":"Tenhola","sequence":"first","affiliation":[{"name":"1Department of PediatricsKymenlaakso Central Hospital, Kotka, Finland"},{"name":"2Department of PediatricsKuopio University Hospital and University of Eastern Finland, Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimo","family":"Voutilainen","sequence":"additional","affiliation":[{"name":"2Department of PediatricsKuopio University Hospital and University of Eastern Finland, Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Reyes","sequence":"additional","affiliation":[{"name":"3Endocrine UnitMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanna","family":"Toiviainen-Salo","sequence":"additional","affiliation":[{"name":"4Department of RadiologyHUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"3Endocrine UnitMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"5Children\u2019s HospitalUniversity of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"6Folkh\u00e4lsan Institute of GeneticsHelsinki, Finland"},{"name":"7Department of Molecular Medicine and SurgeryKarolinska Institutet and Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"2016072718300092000_175.3.211.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610103351505"},{"key":"2016072718300092000_175.3.211.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2003.10.010"},{"key":"2016072718300092000_175.3.211.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2152"},{"key":"2016072718300092000_175.3.211.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1300253"},{"key":"2016072718300092000_175.3.211.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2492"},{"key":"2016072718300092000_175.3.211.6","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1210\/jc.2015-1518","article-title":"Cinacalcet treatment in an adolescent with concurrent 22q11.2 deletion syndrome and familial hypocalciuric hypercalcemia type 3 caused by AP2S1 mutation","volume":"100","author":"Tenhola","year":"2015","journal-title":"Journal of Clinical Endocrinology 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