{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:38:47Z","timestamp":1792820327711,"version":"4.5.0"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"6","funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["Intramural funds"],"award-info":[{"award-number":["Intramural funds"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Research Council","award":["CRC 829-B2,FOR 2722-B1"],"award-info":[{"award-number":["CRC 829-B2,FOR 2722-B1"]}]},{"name":"National Human Genome Research Institute, National Eye Institute, and the National Heart, Lung and Blood Institute","award":["UM1 HG008900"],"award-info":[{"award-number":["UM1 HG008900"]}]},{"name":"National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London","award":["Funds"],"award-info":[{"award-number":["Funds"]}]},{"name":"Fonds de Recherche Qu\u00e9bec \u2013 Sant\u00e9","award":["Fellowship"],"award-info":[{"award-number":["Fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,21]]},"abstract":"<jats:p>\n                    The clinical application of advanced next-generation sequencing technologies is increasingly uncovering novel classes of mutations that may serve as potential targets for precision medicine therapeutics. Here, we show that a deep intronic splice defect in the\n                    <jats:italic>COL6A1<\/jats:italic>\n                    gene, originally discovered by applying muscle RNA sequencing in patients with clinical findings of collagen VI\u2013related dystrophy (COL6-RD), inserts an in-frame pseudoexon into\n                    <jats:italic>COL6A1<\/jats:italic>\n                    mRNA, encodes a mutant collagen \u03b11(VI) protein that exerts a dominant-negative effect on collagen VI matrix assembly, and provides a unique opportunity for splice-correction approaches aimed at restoring normal gene expression. Using splice-modulating antisense oligomers, we efficiently skipped the pseudoexon in patient-derived fibroblast cultures and restored a wild-type matrix. Similarly, we used CRISPR\/Cas9 to precisely delete an intronic sequence containing the pseudoexon and efficiently abolish its inclusion while preserving wild-type splicing. Considering that this splice defect is emerging as one of the single most frequent mutations in COL6-RD, the design of specific and effective splice-correction therapies offers a promising path for clinical translation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.124403","type":"journal-article","created":{"date-parts":[[2019,3,23]],"date-time":"2019-03-23T09:58:42Z","timestamp":1553335122000},"source":"Crossref","is-referenced-by-count":64,"title":["A recurrent COL6A1 pseudoexon insertion causes muscular dystrophy and is effectively targeted by splice-correction therapies"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1690-9270","authenticated-orcid":true,"given":"V\u00e9ronique","family":"Bolduc","sequence":"first","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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