{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:29Z","timestamp":1786976789702,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["512848"],"award-info":[{"award-number":["512848"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23HL136932"],"award-info":[{"award-number":["K23HL136932"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["K08 HG008986"],"award-info":[{"award-number":["K08 HG008986"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["T32 GM007526\u201042"],"award-info":[{"award-number":["T32 GM007526\u201042"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U54HG003273"],"award-info":[{"award-number":["U54HG003273"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1 HG006542"],"award-info":[{"award-number":["UM1 HG006542"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R35NS105078"],"award-info":[{"award-number":["R35NS105078"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The RNA exosome is a multi\u2010subunit complex involved in the processing, degradation, and regulated turnover of RNA. Several subunits are linked to Mendelian disorders, including pontocerebellar hypoplasia (\n                    <jats:italic>EXOSC3<\/jats:italic>\n                    , MIM #614678;\n                    <jats:italic>EXOSC8<\/jats:italic>\n                    , MIM #616081: and\n                    <jats:italic>EXOSC9,<\/jats:italic>\n                    MIM #618065) and short stature, hearing loss, retinitis pigmentosa, and distinctive facies (\n                    <jats:italic>EXOSC2,<\/jats:italic>\n                    MIM #617763). More recently,\n                    <jats:italic>EXOSC5<\/jats:italic>\n                    (MIM *606492) was found to underlie an autosomal recessive neurodevelopmental disorder characterized by developmental delay, hypotonia, cerebellar abnormalities, and dysmorphic facies. An unusual feature of\n                    <jats:italic>EXOSC5<\/jats:italic>\n                    \u2010related disease is the occurrence of complete heart block requiring a pacemaker in a subset of affected individuals. Here, we provide a detailed clinical and molecular characterization of two siblings with microcephaly, developmental delay, cerebellar volume loss, hypomyelination, with cardiac conduction and rhythm abnormalities including sinus node dysfunction, intraventricular conduction delay, atrioventricular block, and ventricular tachycardia (VT) due to compound heterozygous variants in\n                    <jats:italic>EXOSC5<\/jats:italic>\n                    : (1) NM_020158.4:c.341C\u2009&gt;\u2009T (p.Thr114Ile; pathogenic, previously reported) and (2) NM_020158.4:c.302C\u2009&gt;\u2009A (p.Thr101Lys; novel variant). A review of the literature revealed an additional family with biallelic\n                    <jats:italic>EXOSC5<\/jats:italic>\n                    variants and cardiac conduction abnormalities. These clinical and molecular data provide compelling evidence that cardiac conduction abnormalities and arrhythmias are part of the\n                    <jats:italic>EXOSC5<\/jats:italic>\n                    \u2010related disease spectrum and argue for proactive screening due to potential risk of sudden cardiac death.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62352","type":"journal-article","created":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T01:35:00Z","timestamp":1622856900000},"page":"2532-2540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Risk of sudden cardiac death in\n                    <scp>\n                      <i>EXOSC5<\/i>\n                    <\/scp>\n                    \u2010related disease"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6860-372X","authenticated-orcid":false,"given":"Daniel G.","family":"Calame","sequence":"first","affiliation":[{"name":"Division of Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7359-6832","authenticated-orcid":false,"given":"Isabella","family":"Herman","sequence":"additional","affiliation":[{"name":"Division of Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawid M.","family":"Fatih","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulsen","family":"Akay","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Coban\u2010Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, McGovern Medical School University of Texas Health Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-5698","authenticated-orcid":false,"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-3423","authenticated-orcid":false,"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Pediatrics, Faculty of Medicine Kuwait University  Safat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill V.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Radiology Baylor College of Medicine  Houston Texas USA"},{"name":"E.B. Singleton Department of Pediatric Radiology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Fan","sequence":"additional","affiliation":[{"name":"John Welsh Cardiovascular Diagnostic Laboratory Departments of Pediatrics and Pathology &amp; Immunology, Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-9246","authenticated-orcid":false,"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina 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