{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:19:47Z","timestamp":1783005587795,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T00:00:00Z","timestamp":1464134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["1022707"],"award-info":[{"award-number":["1022707"]}]},{"name":"National Health and Medical Research Council of Australia","award":["1031893"],"award-info":[{"award-number":["1031893"]}]},{"name":"National Health and Medical Research Council of Australia","award":["APP1002147"],"award-info":[{"award-number":["APP1002147"]}]},{"name":"National Health and Medical Research Council of Australia","award":["1056285"],"award-info":[{"award-number":["1056285"]}]},{"name":"National Health and Medical Research Council of Australia","award":["633194"],"award-info":[{"award-number":["633194"]}]},{"name":"Victorian Government's Operational Infrastructure Support Program"},{"name":"Muscular Dystrophy NSW"},{"DOI":"10.13039\/501100001232","name":"Royal Australasian College of Physicians","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001232","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"NIH National Human Genome Research Institute","doi-asserted-by":"crossref","award":["U54 HG003067"],"award-info":[{"award-number":["U54 HG003067"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["3R01NS29525"],"award-info":[{"award-number":["3R01NS29525"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and next generation sequencing (NGS) technologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 123 CMD patients were investigated using the traditional approaches of histology, immunohistochemical analysis of muscle biopsy, and candidate gene sequencing. Undiagnosed patients available for further testing were investigated using NGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Muscle biopsy and immunohistochemical analysis found deficiencies of laminin \u03b12, \u03b1\u2010dystroglycan, or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39 of 123). Of 85 patients presenting in the past 20 years, 28 of 51 who lacked a confirmed genetic diagnosis (55%) consented to NGS studies, leading to confirmed diagnoses in a further 11 patients. Using the combination of approaches, a confirmed genetic diagnosis was achieved in 51% (43 of 85). The diagnoses within the cohort were heterogeneous. Forty\u2010five of 59 probands with confirmed or probable diagnoses had variants in genes known to cause CMD (76%), and 11 of 59 (19%) had variants in genes associated with congenital myopathies, reflecting overlapping features of these conditions. One patient had a congenital myasthenic syndrome, and 2 had microdeletions. Within the cohort, 5 patients had variants in novel (<jats:italic>PIGY<\/jats:italic> and <jats:italic>GMPPB<\/jats:italic>) or recently published genes (<jats:italic>GFPT1<\/jats:italic> and <jats:italic>MICU1<\/jats:italic>), and 7 had variants in <jats:italic>TTN<\/jats:italic> or <jats:italic>RYR1<\/jats:italic>, large genes that are technically difficult to Sanger sequence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These data support NGS as a first\u2010line tool for genetic evaluation of patients with a clinical phenotype suggestive of CMD, with muscle biopsy reserved as a second\u2010tier investigation. Ann Neurol 2016;80:101\u2013111<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24687","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T23:32:56Z","timestamp":1462836776000},"page":"101-111","source":"Crossref","is-referenced-by-count":65,"title":["Diagnosis and etiology of congenital muscular dystrophy: We are halfway there"],"prefix":"10.1002","volume":"80","author":[{"given":"Gina L.","family":"O'Grady","sequence":"first","affiliation":[{"name":"Institute for Neuroscience and Muscle Research, Kids Research Institute, Children's Hospital at Westmead Westmead New South Wales Australia"},{"name":"Discipline of Paediatrics and Child Health Faculty of Medicine, University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monkol","family":"Lek","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Muscle Research, Kids Research Institute, Children's Hospital at Westmead 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A.","family":"Sandaradura","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Muscle Research, Kids Research Institute, Children's Hospital at Westmead Westmead New South Wales Australia"},{"name":"Discipline of Paediatrics and Child Health Faculty of Medicine, University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Best","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Muscle Research, Kids Research Institute, Children's Hospital at Westmead Westmead New South Wales Australia"},{"name":"Discipline of Paediatrics and Child Health Faculty of Medicine, University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simranpreet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Muscle Research, Kids Research Institute, Children's Hospital at Westmead Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics PathWest Laboratory Medicine, QEII Medical Centre Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel G.","family":"Laing","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Genomics PathWest Laboratory Medicine, QEII Medical Centre Nedlands Western Australia Australia"},{"name":"Centre for Medical Research University of Western Australia Perth Western Australia Australia"},{"name":"Neurogenetic Unit Harry Perkins Institute of Medical Research Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre UCL Institute of Child Health and Great Ormond Street 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