{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:59:42Z","timestamp":1790240382414,"version":"4.1.0"},"reference-count":14,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acromegaly is usually sporadic but may rarely occur as part of inherited endocrine tumor syndromes, particularly when disease onset is early or multiple family members are affected. Carney complex is an autosomal dominant disorder, most often due to inactivating PRKAR1A mutations, with diverse endocrine and nonendocrine manifestations. We report a 33-year-old man with long-standing acromegaly, growth hormone (GH)-positive pituitary adenoma with focal prolactin positivity, cutaneous and cardiac myxomas, and bilateral large-cell calcifying Sertoli cell tumors. He achieved biochemical remission after endoscopic transsphenoidal surgery. His younger sister had childhood-onset acromegaly requiring pituitary surgery in adolescence and has persistent disease with mildly elevated insulin-like growth factor-1 (IGF-1). She subsequently had a spontaneous pregnancy and delivered a healthy child. Genetic analysis of the index case, sister, and mother identified a novel monoallelic intronic PRKAR1A splice-acceptor variant, c.709-7T&amp;gt;G, in intron 7 near exon 8, causes retention of 6 base pairs from the 3\u2032 end of intron 7, leading to a frameshift and premature truncation, p. (Gly237insPhefs*2), consistent with a likely pathogenic variant. The mother did not develop any endocrine manifestations till date (62 years of age). This report expands the PRKAR1A mutational spectrum and highlights marked intrafamilial phenotypic variability, supporting genetic evaluation in early-onset or familial acromegaly to guide surveillance and family screening.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag244","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T12:46:38Z","timestamp":1786797998000},"source":"Crossref","is-referenced-by-count":0,"title":["Familial acromegaly with a novel\n                    <i>PRKAR1A<\/i>\n                    splice-acceptor variant and marked intrafamilial phenotypic variability"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7247-5492","authenticated-orcid":false,"given":"Vivek","family":"Jha","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER) , Chandigarh 160012 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-6474","authenticated-orcid":false,"given":"Sayka","family":"Barry","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-2598","authenticated-orcid":false,"given":"Debajyoti","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER) , Chandigarh 160012 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3029-4544","authenticated-orcid":false,"given":"Vaishali","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER) , Chandigarh 160012 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-9432","authenticated-orcid":false,"given":"M\u00e1rta","family":"Korbonits","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-1611","authenticated-orcid":false,"given":"Pinaki","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER) , Chandigarh 160012 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"issue":"11","key":"2026092404044408100_luag244-B1","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1172\/JCI39375","article-title":"Acromegaly pathogenesis and treatment","volume":"119","author":"Melmed","year":"2009","journal-title":"J Clin Invest"},{"issue":"3","key":"2026092404044408100_luag244-B2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.beem.2010.03.001","article-title":"The genetics of pituitary adenomas","volume":"24","author":"Vandeva","year":"2010","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"3","key":"2026092404044408100_luag244-B3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1172\/JCI118467","article-title":"Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2","volume":"97","author":"Stratakis","year":"1996","journal-title":"J Clin Invest"},{"issue":"4","key":"2026092404044408100_luag244-B4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/humu.21178","article-title":"Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update","volume":"31","author":"Horvath","year":"2010","journal-title":"Hum Mutat"},{"issue":"4","key":"2026092404044408100_luag244-B5","doi-asserted-by":"crossref","first-page":"M85","DOI":"10.1530\/EJE-15-0209","article-title":"Carney complex: an update","volume":"173","author":"Correa","year":"2015","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2026092404044408100_luag244-B6","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1158\/1078-0432.CCR-07-1155","article-title":"Large deletions of the PRKAR1A gene in carney complex","volume":"14","author":"Horvath","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"3","key":"2026092404044408100_luag244-B7","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11102-006-0265-2","article-title":"Pituitary pathology in patients with carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities","volume":"9","author":"Boikos","year":"2006","journal-title":"Pituitary"},{"issue":"9","key":"2026092404044408100_luag244-B8","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1210\/jcem.86.9.7903","article-title":"Clinical and molecular features of the carney complex: diagnostic criteria and recommendations for patient evaluation","volume":"86","author":"Stratakis","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2026092404044408100_luag244-B9","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.beem.2009.05.008","article-title":"The epidemiology and genetics of pituitary adenomas","volume":"23","author":"Daly","year":"2009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"5","key":"2026092404044408100_luag244-B10","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s11102-019-00974-8","article-title":"Acromegaly in carney complex","volume":"22","author":"Cuny","year":"2019","journal-title":"Pituitary"},{"issue":"2","key":"2026092404044408100_luag244-B11","first-page":"59","article-title":"Acromegaly as an expression of a rare disease: description of an unusual clinical case of carney Complex","volume":"9","author":"Costa","year":"2020","journal-title":"Case Rep Clin Med"},{"issue":"1","key":"2026092404044408100_luag244-B12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1750-1172-1-21","article-title":"Carney complex (CNC)","volume":"1","author":"Bertherat","year":"2006","journal-title":"Orphanet J Rare Dis"},{"issue":"9","key":"2026092404044408100_luag244-B13","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/s41588-024-01872-x","article-title":"Global impact of unproductive splicing on human gene expression","volume":"56","author":"Fair","year":"2024","journal-title":"Nat Genet"},{"issue":"6","key":"2026092404044408100_luag244-B14","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1086\/344579","article-title":"Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD","volume":"71","author":"Groussin","year":"2002","journal-title":"Am J Hum Genet"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/10\/luag244\/71372319\/luag244.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/10\/luag244\/71372319\/luag244.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:04:50Z","timestamp":1790237090000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luag244\/8833355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":14,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luag244","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,9,3]]},"article-number":"luag244"}}