{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:56:36Z","timestamp":1791467796234,"version":"4.3.4"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by inactivating germline variants in DNA mismatch repair genes. Here, we describe a woman who developed colorectal, gastric, and endometrial cancers and was found to have a rare missense variant, MLH1:c.545G\u00a0&amp;gt;\u00a0T\/p.Arg182Met. The variant, which was located at the last nucleotide of MLH1exon 6, was initially reported by a clinical testing laboratory as being a variant of uncertain significance. In silico analyses predicted that it would cause splicing aberration, and reverse-transcription polymerase chain reaction analysis of total RNA from the patient\u2019s peripheral blood cells identified an aberrant MLH1 transcript that skipped the entire exon 6 and caused generation of a premature stop codon (p.Glu153Phefs*8). In accordance with the American College of Medical Genetics and Genomics\/Association for Molecular Pathology guidelines, we reclassified the variant as likely pathogenic. Further additional analysis enabled carrier diagnosis in the patient\u2019s relatives.<\/jats:p>\n                  <jats:p>Genetics summary<\/jats:p>\n                  <jats:p>Disorder: Lynch syndrome<\/jats:p>\n                  <jats:p>Ethnicity of the patient: Japanese<\/jats:p>\n                  <jats:p>Gene: MLH1 (19 exons)<\/jats:p>\n                  <jats:p>GenBank accession number: NM_000249.4<\/jats:p>\n                  <jats:p>Chromosomal assignment: 3p21.3<\/jats:p>\n                  <jats:p>Type of DNA variant: a germline splice aberration variant<\/jats:p>\n                  <jats:p>Mutation: c.545G\u00a0&amp;gt;\u00a0T in exon 6 of MLH1<\/jats:p>\n                  <jats:p>Methods of mutation detection: PCR-sequencing, RT-PCR<\/jats:p>","DOI":"10.1093\/jjco\/hyag101","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T20:49:21Z","timestamp":1783370961000},"page":"1264-1271","source":"Crossref","is-referenced-by-count":0,"title":["A Lynch syndrome patient with multiple cancers who was found to have a novel pathogenic variant generating aberrant splicing of\n                    <i>MLH1<\/i>"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1365-2696","authenticated-orcid":false,"given":"Ayumi","family":"Abe","sequence":"first","affiliation":[{"name":"Clinical Genetics Center, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]},{"name":"Department of Clinical Genetics, Juntendo University, Graduate School of Medicine , Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of Medicine , Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimio","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Clinical Genetics Center, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]},{"name":"Department of Endocrinology and Metabolism, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudai","family":"Fukui","sequence":"additional","affiliation":[{"name":"Clinical Genetics Center, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]},{"name":"Department of Gastroenterological Surgery, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Fujii","sequence":"additional","affiliation":[{"name":"Keio Clinic for Diagnostic Digital Pathology , Daikyocho 30-1, Shinjyuku-ku, Tokyo, 160-0015 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Ikemura","sequence":"additional","affiliation":[{"name":"Department of Pathology, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaku","family":"Kuge","sequence":"additional","affiliation":[{"name":"Department of Pathology, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Kuroyanagi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Center, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]},{"name":"Department of Gastroenterological Surgery, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of Medicine , Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Arai","sequence":"additional","affiliation":[{"name":"Clinical Genetics Center, Toranomon Hospital , Toranomon 2-2-2 Minato-ku, Tokyo, 105-8470 ,","place":["Japan"]},{"name":"Department of Clinical Genetics, Juntendo University, Graduate School of Medicine , Hongo 2-1-1, Bunkyo-ku, Tokyo, 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