{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:37Z","timestamp":1753869697391,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007606","name":"Aarhus Universitetshospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pathogenic variants in <jats:italic>STK11<\/jats:italic>, also designated as <jats:italic>LKB1<\/jats:italic>, cause Peutz\u2013Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation changes, polyposis, and a high risk of cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A male meeting the clinical diagnostic criteria for Peutz\u2013Jeghers syndrome underwent next\u2010generation sequencing. To validate the predicted splicing impact of a detected <jats:italic>STK11<\/jats:italic> variant, we performed RNA\u2010Seq on mRNA extracted from patient\u2010derived Epstein\u2010Barr virus\u2010transformed lymphocytes treated with cycloheximide to inhibit nonsense\u2010mediated decay ex vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Blood testing identified a novel single\u2010nucleotide substitution, NM_000455.4:c.735\u201010C&gt;A, at the end of the 3\u2032 polypyrimidine tract of intron five in <jats:italic>STK11<\/jats:italic>. RNA\u2010Seq confirmed a predicted eight base pair insertion in the mRNA transcript. Following inhibition of nonsense\u2010mediated decay, the out\u2010of\u2010frame insertion was detected in 50% of all RNA\u2010Seq reads. This confirmed a strong, deleterious splicing impact of the variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We characterized a novel likely pathogenic germline variant in intron five of <jats:italic>STK11<\/jats:italic> associated with Peutz\u2013Jeghers syndrome. The study highlights RNA\u2010Seq as a useful supplement in hereditary cancer predisposition testing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1381","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T09:05:56Z","timestamp":1592903156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Deleterious mis\u2010splicing of <i>STK11<\/i> caused by a novel single\u2010nucleotide substitution in the 3\u2032 polypyrimidine tract of intron five"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-1043","authenticated-orcid":false,"given":"Thorkild","family":"Terkelsen","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5213-7349","authenticated-orcid":false,"given":"Ole H.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-4205","authenticated-orcid":false,"given":"S\u00f8ren","family":"Vang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6205-6355","authenticated-orcid":false,"given":"Uffe B.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9038-2003","authenticated-orcid":false,"given":"Friedrik","family":"Wikman","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1211"},{"key":"e_1_2_9_3_1","unstructured":"Andrews S.(2010).FastQC [Computer software]. 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