{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:29:15Z","timestamp":1790270955768,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T00:00:00Z","timestamp":1209340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Context\u2002<\/jats:bold> Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome (OMIM 160980). About 70% of cases are familiar; most have mutations of the <jats:italic>PRKAR1A<\/jats:italic> gene on chromosome 17q22\u201324. There is little phenotype\u2013genotype correlation known to date.<\/jats:p><jats:p><jats:bold>Objective\u2002<\/jats:bold> To study the genotype\u2013phenotype correlation in a family with newly diagnosed CNC and three generations of subjects bearing the same <jats:italic>PRKAR1A<\/jats:italic> mutation. The proband was diagnosed with hepatocellular carcinoma, a tumour that appears to be associated with CNC.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> The study consisted of clinical and genetic analysis of a total of 10 individuals belonging to a large Italian family.<\/jats:p><jats:p><jats:bold>Patients\u2002<\/jats:bold> The index case was referred for <jats:italic>PRKAR1A<\/jats:italic> gene mutation analysis because he met the diagnostic criteria for a clinical diagnosis of CNC.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> The <jats:italic>PRKAR1A<\/jats:italic>\u2010inactivating mutation c.502\u00a0+1G\u00a0&gt;\u00a0A in the intron 5 splice\u2010donor site was detected after bidirectional sequencing of germline DNA. The mutation causes a frameshift in the transcribed sequence and a nonsense mRNA that was shown to be degraded; this leads to <jats:italic>PRKAR1A<\/jats:italic> haploinsufficiency in all tissues. All available relatives were screened first by DNA testing and, if the latter was positive, by clinical, biochemical and imaging means.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> A novel <jats:italic>PRKAR1A <\/jats:italic>mutation with an apparently low penetrance and variable expression is reported; the same mutation is also associated with a hepatocellular carcinoma. This is the first time a <jats:italic>PRKAR1A<\/jats:italic> mutation is reported in individuals who were diagnosed with CNC after retrospective family screening and following the identification of a proband; the finding has implications for genetic counselling on <jats:italic>PRKAR1A<\/jats:italic> and\/or CNC.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2008.03286.x","type":"journal-article","created":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T07:54:11Z","timestamp":1209369251000},"page":"751-755","source":"Crossref","is-referenced-by-count":21,"title":["A novel <i>PRKAR1A<\/i> mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations"],"prefix":"10.1111","volume":"69","author":[{"given":"Monia","family":"Gennari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine A.","family":"Stratakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anelia","family":"Hovarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Pirazzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cicognani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,14]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198507000-00007"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.20.3037"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.9.7903"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(05)70244-8"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-1-21"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e32801195eb"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/79238"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10841"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(91)90075-W"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00452-6"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0110265"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3620"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028043"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0580"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405535101"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2708"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1159\/000095527"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90432-X"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90433-Y"},{"key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"222","DOI":"10.5858\/2004-128-222-FHCOYA","article-title":"Fibrolamellar hepatocellular carcinoma occurring, 5 years after hepatocellular adenoma in a, 14\u2010year\u2010old girl: a case report with comparative genomic hybridization analysis","volume":"128","author":"Terracciano L.M.","year":"2004","journal-title":"Archives of Pathology and Laboratory Medicine"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2265.2008.03286.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2265.2008.03286.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T20:56:42Z","timestamp":1697230602000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2265.2008.03286.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,14]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["10.1111\/j.1365-2265.2008.03286.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2265.2008.03286.x","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,14]]}}}