Journal article
Diagnosis and etiology of congenital muscular dystrophy: We are halfway there
GL O'Grady, M Lek, SR Lamande, L Waddell, EC Oates, J Punetha, R Ghaoui, SA Sandaradura, H Best, S Kaur, M Davis, NG Laing, F Muntoni, E Hoffman, DG MacArthur, NF Clarke, S Cooper, K North
Annals of Neurology | WILEY | Published : 2016
DOI: 10.1002/ana.24687
Abstract
Objective: To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and next generation sequencing (NGS) technologies. Methods: 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. Results: Muscle biopsy and immunohistochemical analysis found deficiencies of laminin α2, α-dystroglycan, or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39 of 123). Of 85 patien..
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Awarded by Royal Australasian College of Physicians
Funding Acknowledgements
Supported by the National Health and Medical Research Council of Australia (1022707, 1031893, N.F.C, N.G.L., K.N.; APP1002147, N.G.L.; 1056285, G.L.O.; 633194, E.C.O.) and the Victorian Government's Operational Infrastructure Support Program. G.L.O. received funding from Muscular Dystrophy NSW and the Royal Australasian College of Physicians. Exome sequencing was supported by grants from the National Human Genome Research Institute (NIH) (Medical Sequencing Program grant U54 HG003067 to the Broad Institute principal investigator, E.L.). Targeted sequencing was supported by the NIH (3R01NS29525, E.H.).We thank Muscular Dystrophy UK, the Biomedical Research Centre, and the National Specialist Commissioning Team for the support of the Dubowitz Neuromuscular Centre at Great Ormond Street Hospital.