{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:25Z","timestamp":1753869685623,"version":"3.41.2"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["293587"],"award-info":[{"award-number":["293587"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000912","name":"March of Dimes Foundation","doi-asserted-by":"publisher","award":["6\u2010FY14 422"],"award-info":[{"award-number":["6\u2010FY14 422"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS109149"],"award-info":[{"award-number":["R01NS109149"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital muscular dystrophy type 1A (MDC1A), also termed merosin\u2010deficient congenital muscular dystrophy (CMD), is a severe form of CMD caused by mutations in the laminin \u03b12 gene (<jats:italic>LAMA2<\/jats:italic>). Of the more than 300 likely pathogenic variants found in the Leiden Open Variant Database, the majority are truncating mutations leading to complete <jats:italic>LAMA2<\/jats:italic> loss of function, but multiple copy number variants (CNVs) have also been reported with variable frequency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected a cohort of individuals diagnosed with likely MDC1A and sought to identify both single nucleotide variants and small and larger CNVs via exome sequencing by extending the analysis of sequencing data to detect splicing changes and CNVs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Standard exome analysis identified multiple novel <jats:italic>LAMA2<\/jats:italic> variants in our cohort, but only four cases carried biallelic variants. Since likely truncating <jats:italic>LAMA2<\/jats:italic> variants are often found in heterozygosity without a second allele, we performed additional splicing and CNV analysis on exome data and identified one splice change outside of the canonical sequences and three CNVs, in the remaining four cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings support the expectation that a portion of MDC1A cases may be caused by at least one CNV allele and show how these changes can be effectively identified by additional analysis of existing exome data.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1387","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T22:12:21Z","timestamp":1600294341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel mutation identification and copy number variant detection via exome sequencing in congenital muscular dystrophy"],"prefix":"10.1002","volume":"8","author":[{"given":"Edmund S.","family":"Cauley","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Institute for Neuroscience The George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Pittman","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Institute St. George\u2019s, University of London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati","family":"Mummidivarpu","sequence":"additional","affiliation":[{"name":"Departments of Pharmaceutical Sciences and Biomedical Engineering Binghamton University\u2010SUNY Binghamton NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan G.","family":"Karimiani","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Institute St. George\u2019s, University of London London United Kingdom"},{"name":"Innovative Medical Research Center Islamic Azad University Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Institute for Neuroscience The George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Moroni","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Boostani","sequence":"additional","affiliation":[{"name":"Department of Neurology Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Podini","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences The George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Mora","sequence":"additional","affiliation":[{"name":"Division of Neuromuscular Diseases and Neuroimmunology Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0151-6482","authenticated-orcid":false,"given":"Yalda","family":"Jamshidi","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Institute St. George\u2019s, University of London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Departments of Pharmaceutical Sciences and Biomedical Engineering Binghamton University\u2010SUNY Binghamton NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-1096","authenticated-orcid":false,"given":"M. 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