{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:33:25Z","timestamp":1772580805550,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Point mutations of the <jats:italic>PRKAR1A<\/jats:italic> gene are a genetic cause of Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), but in 30% of the patients no mutation is detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Set up a routine-based technique for systematic detection of large deletions or duplications of this gene and functionally characterize these mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multiplex ligation-dependent probe amplification (MLPA) of the 12 exons of the <jats:italic>PRKAR1A<\/jats:italic> gene was validated and used to detect large rearrangements in 13 typical CNC and 39 confirmed or putative PPNAD without any mutations of the gene. An in-frame deletion was characterized by western blot and bioluminescence resonant energy transfer technique for its interaction with the catalytic subunit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MLPA allowed identification of exons 3\u20136 deletion in three patients of a family with typical CNC. The truncated protein is expressed, but rapidly degraded, and does not interact with the protein kinase A catalytic subunit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MLPA is a powerful technique that may be used following the lack of mutations detected by direct sequencing in patients with bona fide CNC or PPNAD. We report here one such new deletion, as an example. However, these gene defects are not a frequent cause of CNC or PPNAD.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-13-0740","type":"journal-article","created":{"date-parts":[[2013,10,22]],"date-time":"2013-10-22T02:28:27Z","timestamp":1382408907000},"page":"151-160","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":12,"title":["Systematic screening for PRKAR1A gene rearrangement in Carney complex: identification and functional characterization of a new in-frame deletion"],"prefix":"10.1093","volume":"170","author":[{"given":"M","family":"Guillaud Bataille","sequence":"first","affiliation":[]},{"given":"Y","family":"Rhayem","sequence":"additional","affiliation":[]},{"given":"S B","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"R","family":"Lib\u00e9","sequence":"additional","affiliation":[]},{"given":"M","family":"Dambrun","sequence":"additional","affiliation":[]},{"given":"C","family":"Chevalier","sequence":"additional","affiliation":[]},{"given":"M","family":"Nigou","sequence":"additional","affiliation":[]},{"given":"C","family":"Auzan","sequence":"additional","affiliation":[]},{"given":"M O","family":"North","sequence":"additional","affiliation":[]},{"given":"J","family":"Sa","sequence":"additional","affiliation":[]},{"given":"L","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"P","family":"Salpea","sequence":"additional","affiliation":[]},{"given":"A","family":"Horvath","sequence":"additional","affiliation":[]},{"given":"C A","family":"Stratakis","sequence":"additional","affiliation":[]},{"given":"N","family":"Hamzaoui","sequence":"additional","affiliation":[]},{"given":"J","family":"Bertherat","sequence":"additional","affiliation":[]},{"given":"E","family":"Clauser","sequence":"additional","affiliation":[]}],"member":"286","reference":[{"issue":"1","key":"1_10460204","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/79238","volume":"26","author":"Kirschner","year":"2000","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"20","key":"2_10581892","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1093\/hmg\/9.20.3037","volume":"9","author":"Kirschner","year":"2000","journal-title":"Human Molecular Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0964-6906","issn-type":"print"},{"issue":"4","key":"3_13545103","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/00005792-198507000-00007","volume":"64","author":"Carney","year":"1985","journal-title":"Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0025-7974","issn-type":"print"},{"issue":"5","key":"4_21588638","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1210\/jc.2005-2708","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; 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