{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:37:36Z","timestamp":1791992256997,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Mutations in the nuclear envelope genes encoding\n              <jats:italic>LMNA<\/jats:italic>\n              and\n              <jats:italic>EMD<\/jats:italic>\n              are responsible for Emery-Dreifuss muscular dystrophy. However,\n              <jats:italic>LMNA<\/jats:italic>\n              mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of\n              <jats:italic>EMD<\/jats:italic>\n              mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with\n              <jats:italic>EMD<\/jats:italic>\n              mutations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We identified 3 X-linked recessive\n              <jats:italic>EMD<\/jats:italic>\n              mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with\n              <jats:italic>EMD<\/jats:italic>\n              has never been reported, we further genetically screened 102 LVNC patients and found a frameshift\n              <jats:italic>EMD<\/jats:italic>\n              mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male\n              <jats:italic>EMD<\/jats:italic>\n              mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.120.008712","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T23:46:12Z","timestamp":1596066372000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Cardiac Emerinopathy"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8195-4700","authenticated-orcid":true,"given":"Taisuke","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Omics Research Center (T.I., N.M.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Human Genetics (H.M., K.-I.Y.), Nagasaki University Graduate School of Biomedical Sciences, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Barc","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, France (J.B., J.-J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-5012","authenticated-orcid":true,"given":"Masanori P.","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan (M.P.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-9053","authenticated-orcid":true,"given":"Keiichi","family":"Hirono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Japan (K.H., F.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenori","family":"Terada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shin-Oyama City Hospital, Japan (S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kowase","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Yokohama Rosai Hospital, Japan (S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Akita University Graduate School of Medicine, Japan (T.S., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan (Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Yui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Tsukuba University, Japan (Y.Y., A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimie","family":"Ohkubo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nihon University School of Medicine, Tokyo, Japan (K.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kimoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology (H.K.), Nagasaki University Graduate School of Biomedical Sciences, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Akita University Graduate School of Medicine, Japan (T.S., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, University of Toyama, Japan (Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1779-7282","authenticated-orcid":true,"given":"Takeshi","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (T.A.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"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 Bioscience and Genetics (S.O.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Chishaki","sequence":"additional","affiliation":[{"name":"Clinical Nursing Laboratory, School of Medicine, Kyushu University, Fukuoka, Japan (A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-8973","authenticated-orcid":true,"given":"Wataru","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan (W.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-2339","authenticated-orcid":true,"given":"Minoru","family":"Horie","sequence":"additional","affiliation":[{"name":"Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Ohtsu, Japan (M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-9206","authenticated-orcid":true,"given":"Fukiko","family":"Ichida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Japan (K.H., F.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-4601","authenticated-orcid":true,"given":"Akihiko","family":"Nogami","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Tsukuba University, Japan (Y.Y., A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koh-Ichiro","family":"Yoshiura","sequence":"additional","affiliation":[{"name":"Department of Human Genetics (H.M., K.-I.Y.), Nagasaki University Graduate School of Biomedical Sciences, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Schott","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, France (J.B., J.-J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-672X","authenticated-orcid":true,"given":"Naomasa","family":"Makita","sequence":"additional","affiliation":[{"name":"Omics Research Center (T.I., N.M.), National Cerebral and Cardiovascular Center, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","first-page":"1367","volume-title":"In: Handbook of Clinical 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