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The Impact of Next-Generation Sequencing on the Diagnosis, Treatment, and Prevention of Hereditary Neuromuscular Disorders

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Abstract

The impact of high-throughput sequencing in genetic neuromuscular disorders cannot be overstated. The ability to rapidly and affordably sequence multiple genes simultaneously has enabled a second golden age of Mendelian disease gene discovery, with flow-on impacts for rapid genetic diagnosis, evidence-based treatment, tailored therapy development, carrier-screening, and prevention of disease recurrence in families. However, there are likely many more neuromuscular disease genes and mechanisms to be discovered. Many patients and families remain without a molecular diagnosis following targeted panel sequencing, clinical exome sequencing, or even genome sequencing. Here we review how massively parallel, or next-generation, sequencing has changed the field of genetic neuromuscular disorders, and anticipate future benefits of recent technological innovations such as RNA-seq implementation and detection of tandem repeat expansions from short-read sequencing.

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  1. Neurogenetic Diseases Group, Centre for Medical Research, QEII Medical Centre, University of Western Australia, 6 Verdun St, Nedlands, WA, 6009, Australia

    Sarah J. Beecroft, Samantha Edwards, Hayley Goullée, Nigel G. Laing & Gianina Ravenscroft

  2. Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, 6009, Australia

    Sarah J. Beecroft, Samantha Edwards, Hayley Goullée, Nigel G. Laing & Gianina Ravenscroft

  3. Neurogenetic Clinic, Royal Perth Hospital, Perth, Australia

    Phillipa J. Lamont & Nigel G. Laing

  4. Neurogenetic Unit, Department of Diagnostic Genomics, PP Block, QEII Medical Centre, Nedlands, WA, Australia

    Mark R. Davis

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SJB is funded by The Fred Liuzzi Foundation (TFLF) (Melbourne, Australia). NGL (APP1117510) and GR (APP1122952) are supported by the Australian National Health and Medical Research Council (NHMRC).

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Beecroft, S.J., Lamont, P.J., Edwards, S. et al. The Impact of Next-Generation Sequencing on the Diagnosis, Treatment, and Prevention of Hereditary Neuromuscular Disorders. Mol Diagn Ther 24, 641–652 (2020). https://doi.org/10.1007/s40291-020-00495-2

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