{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:05:29Z","timestamp":1764137129801,"version":"3.46.0"},"reference-count":10,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18kk0205004"],"award-info":[{"award-number":["JP18kk0205004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015322","name":"National Cancer Center Japan","doi-asserted-by":"publisher","award":["31\u2010A\u20102"],"award-info":[{"award-number":["31\u2010A\u20102"]}],"id":[{"id":"10.13039\/100015322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K07339"],"award-info":[{"award-number":["JP18K07339"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lynch syndrome (LS) is an autosomal\u2010dominant hereditary cancer syndrome caused by defective mismatch repair (MMR) genes. This report presents two cases of LS with rare intronic variants in MLH1 and MSH2 that affect splicing, leading to diagnostic challenges and implications for management. The first case involves a 50\u2010year\u2010old woman with a history of colorectal and endometrial cancers, identified with a MSH2 c.2458+976A&gt;G variant, resulting in pseudo\u2010exon inclusion. The second case describes a 70\u2010year\u2010old woman with synchronous endometrial and cecal cancers, carrying an MLH1 c.545+4_545+5del variant, which caused exon 6 skipping. Both cases have strong familial and\/or medical histories of LS\u2010related cancers, but no pathogenic variant has been detected by conventional genetic testing. In these cases, RNA sequencing played a crucial role in establishing a definitive diagnosis. These findings highlight the need for genetic testing beyond conventional exon\u2010focused sequencing to ensure accurate diagnosis and management.<\/jats:p>","DOI":"10.1111\/jog.70117","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:23:24Z","timestamp":1761783804000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rare Intronic Variants Altering Splicing Cause Lynch Syndrome: Two Case Reports"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2587-1502","authenticated-orcid":false,"given":"Yumi","family":"Takimoto","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Hyogo Medical University, School of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-6313","authenticated-orcid":false,"given":"Hiroshi","family":"Tsubamoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Hyogo Medical University, School of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Wakatsuki","sequence":"additional","affiliation":[{"name":"Division of Molecular Diagnosis and Cancer Prevention Saitama Cancer Center  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riyo","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Sakai City Medical Center Nursing Department  Osaka Japan"},{"name":"Division of Cancer Treatment Toyonaka Municipal Hospital  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gou","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Diagnosis and Cancer Prevention Saitama Cancer Center  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Sawai","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Hyogo Medical University, School of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuo","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hyogo Medical University, School of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment Toyonaka Municipal Hospital  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Mabuchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Hyogo Medical University, School of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiwamu","family":"Akagi","sequence":"additional","affiliation":[{"name":"Division of Molecular Diagnosis and Cancer Prevention Saitama Cancer Center  Saitama Japan"},{"name":"Center for Genomic Diagnosis International University of Health and Welfare (IUHW), Narita Hospital  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyz031"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/tog.12706"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04031-w"},{"issue":"1","key":"e_1_2_12_5_1","first-page":"13","article-title":"Study for Establishment of Effective Screening and Diagnosis for Lynch Syndrome: Dial Study, Construction of Integrated Database of Clinical and Genetic Information for Lynch Syndrome in Japan","volume":"19","author":"Akagi K.","year":"2019","journal-title":"Journal of Family Tumors"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyv103"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.08.041"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-011-9427-0"},{"issue":"3","key":"e_1_2_12_9_1","article-title":"Utility of Clinical RNA Sequencing to Resolve Variants of Uncertain Significance in a Case Series","volume":"25","author":"Waldman Y. Y.","year":"2023","journal-title":"Genetics in Medicine"},{"key":"e_1_2_12_10_1","article-title":"Whole Genome Sequencing Completes the Molecular Genetic Testing Workflow of Patients With Lynch Syndrome","volume":"13","author":"Horti\u2010Oravecz K.","year":"2023","journal-title":"Scientific Reports"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34025"}],"container-title":["Journal of Obstetrics and Gynaecology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jog.70117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:01:16Z","timestamp":1764136876000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/jog.70117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":10,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/jog.70117"],"URL":"https:\/\/doi.org\/10.1111\/jog.70117","archive":["Portico"],"relation":{},"ISSN":["1341-8076","1447-0756"],"issn-type":[{"type":"print","value":"1341-8076"},{"type":"electronic","value":"1447-0756"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70117"}}