{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:34:23Z","timestamp":1787510063209,"version":"build-2736575974"},"reference-count":17,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2020,10]]},"abstract":"\n Background:<\/jats:title>\n \n LMNA<\/jats:italic>\n is a known causative gene of dilated cardiomyopathy and familial conduction disturbance. Nonsense-mediated mRNA decay, normally caused by nonsense mutations, is a safeguard process to protect cells from deleterious effects of inappropriate proteins from mutated genes. Nonsense-mediated mRNA decay induced by nonstop codon mutations is rare. We investigated the effect of an\n LMNA<\/jats:italic>\n missense mutation identified in 2 families affected by cardiac laminopathy.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Genomic DNA and total RNA were isolated from patients\u2019 peripheral blood lymphocytes or cardiac tissue.\n LMNA<\/jats:italic>\n -coding exons were screened by direct sequencing. Complementary DNAs were generated by a reverse transcription-polymerase chain reaction from total RNA. Quantitative polymerase chain reaction was performed to quantify the\n LMNA<\/jats:italic>\n complementary DNA amount by using specific primers for lamins A and C. A minigene splicing reporter experiment was performed to assess the effect of detected variants on RNA splicing. The protein expressions of both isoforms were analyzed by Western blotting.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n We detected a missense variant c.936 G>C (p. Q312H) at the end of exon 5 of\n LMNA<\/jats:italic>\n by genomic DNA sequencing in 2 unrelated families affected by dilated cardiomyopathy and cardiac conduction disturbance. This variant was previously reported in a French family suffering from muscular dystrophy and cardiac conduction disturbance. Sequencing of complementary DNA demonstrated that the mutated allele was absent. By quantitative polymerase chain reaction assay, we confirmed a 90% reduction in\n LMNA<\/jats:italic>\n complementary DNA. The minigene splicing reporter assay demonstrated a splicing error by the variant. Western blot analysis revealed that lamin A and C expressions were reduced far >50%.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n We report an\n LMNA<\/jats:italic>\n missense mutation found in 2 families, which disrupted a normal splicing site, led to nonsense-mediated mRNA decay, and resulted in severe cardiac laminopathy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circgen.119.002853","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T19:17:22Z","timestamp":1597951042000},"page":"435-443","source":"Crossref","is-referenced-by-count":25,"title":["LMNA<\/i>\n Missense Mutation Causes Nonsense-Mediated mRNA Decay and Severe Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6125-0789","authenticated-orcid":true,"given":"Koichi","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine (K.K., S.O., M.F., T.O., M.H.), Shiga University of Medical Science, Otsu."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-8896","authenticated-orcid":true,"given":"Seiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (K.K., S.O., M.F., T.O., M.H.), Shiga University of Medical Science, Otsu."},{"name":"Center for Epidemiologic Research in Asia (S.O., M.H.), Shiga University of Medical Science, Otsu."},{"name":"Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita (S.O., K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7015-5839","authenticated-orcid":true,"given":"Keiko","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita (S.O., K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-4053","authenticated-orcid":true,"given":"Megumi","family":"Fukuyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (K.K., S.O., M.F., T.O., M.H.), Shiga University of Medical Science, Otsu."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9471-5335","authenticated-orcid":true,"given":"Takeru","family":"Makiyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (T.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (K.K., S.O., M.F., T.O., M.H.), Shiga University of Medical Science, Otsu."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-2339","authenticated-orcid":true,"given":"Minoru","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (K.K., S.O., M.F., T.O., M.H.), Shiga University of Medical Science, Otsu."},{"name":"Center for Epidemiologic Research in Asia (S.O., M.H.), Shiga University of Medical Science, Otsu."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1652708"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01724-2"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199912023412302"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-18-0339"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1048803"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2013.12.011"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-3787(05)84972-0"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001603"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.12.015"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2018.05.028"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.08.058"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02954-6"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz259"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-007-0275-1"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.08.024"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09929-w"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000125524.34234.13"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","deposited":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T09:52:51Z","timestamp":1603792371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.119.002853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1161\/CIRCGEN.119.002853"],"URL":"https:\/\/doi.org\/10.1161\/circgen.119.002853","relation":{},"ISSN":["2574-8300","2574-8300"],"issn-type":[{"value":"2574-8300","type":"print"},{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}