{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:36:13Z","timestamp":1787016973997,"version":"build-2736575974"},"reference-count":13,"publisher":"BMJ","issue":"4","funder":[{"name":"Ambry Genetics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2022,4,12]]},"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>\n                    Despite advances in genetic testing for Lynch syndrome, nearly one quarter of mismatch repair-deficient (MMRd) colorectal and endometrial cancers remain unexplained. When added to germline DNA testing, RNA sequencing can increase diagnostic yield, improve variant classification and reduce variants of uncertain significance. Here, we describe two cases where RNA sequencing uncovered likely pathogenic\n                    <jats:italic>MSH2<\/jats:italic>\n                    variants in families with MMRd tumours that were initially unexplained following comprehensive genetic testing for Lynch syndrome.\n                  <\/jats:p>","DOI":"10.1136\/bcr-2022-249580","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T11:57:37Z","timestamp":1651233457000},"page":"e249580","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["RNA sequencing uncovers clinically actionable germline intronic\n                    <i>MSH2<\/i>\n                    variants in previously unresolved Lynch syndrome families"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-9046","authenticated-orcid":false,"given":"Kelly","family":"Fulk","sequence":"first","affiliation":[{"name":"Ambry Genetics Corp, Aliso Viejo, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Turner","sequence":"additional","affiliation":[{"name":"Inova Primary Care, Falls Church, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Eppolito","sequence":"additional","affiliation":[{"name":"Piedmont Healthcare Inc, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Krukenberg","sequence":"additional","affiliation":[{"name":"Community Health Network Inc, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"2025082722065140000_15.4.e249580.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105698"},{"key":"2025082722065140000_15.4.e249580.2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00696"},{"key":"2025082722065140000_15.4.e249580.3","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ygyno.2020.10.012","article-title":"Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients","volume":"160","author":"Hampel","year":"2021","journal-title":"Gynecol Oncol"},{"key":"2025082722065140000_15.4.e249580.4","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1053\/j.gastro.2019.01.248","article-title":"Rna analysis identifies pathogenic duplications in MSH2 in patients with Lynch syndrome","volume":"156","author":"Conner","year":"2019","journal-title":"Gastroenterology"},{"key":"2025082722065140000_15.4.e249580.5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00286"},{"key":"2025082722065140000_15.4.e249580.6","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.13900","article-title":"Assessment of diagnostic outcomes of RNA genetic testing for hereditary cancer","volume":"2","author":"Karam","year":"2019","journal-title":"JAMA Netw Open"},{"key":"2025082722065140000_15.4.e249580.7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cll.2020.02.004","article-title":"The clinical application of RNA sequencing in genetic diagnosis of Mendelian disorders","volume":"40","author":"Stenton","year":"2020","journal-title":"Clin Lab Med"},{"key":"2025082722065140000_15.4.e249580.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-020-0109-y"},{"key":"2025082722065140000_15.4.e249580.9","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2025082722065140000_15.4.e249580.10","doi-asserted-by":"publisher","DOI":"10.1002\/path.1858"},{"key":"2025082722065140000_15.4.e249580.11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03485.x"},{"key":"2025082722065140000_15.4.e249580.12","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.435"},{"key":"2025082722065140000_15.4.e249580.13","unstructured":"National Comprehensive Cancer Network . NCCN clinical practice guidelines in oncology (NCCN Guidelines\u00ae) for Genetic\/Familial high-risk assessment: colorectal V1.2021. Available: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/genetics_colon.pdf [Accessed 24 Sep 2021]."}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2022-249580","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T05:06:59Z","timestamp":1756357619000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2022-249580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":13,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,29]]},"published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1136\/bcr-2022-249580"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2022-249580","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4]]}}}