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Approaches to genetic diagnosis in neuromuscular conditions in the era of next generation sequencing
  1. Hooi Ling Teoh1,2,
  2. Hugo Sampaio1,2,
  3. Tony Roscioli3,4,5,
  4. Michelle Farrar1,2
  1. 1School of Women's and Children's Health, UNSW Medicine, University of New South Wales, Sydney, New South Wales, Australia
  2. 2Department of Pediatric Neurology, Sydney Children's Hospital, Randwick, New South Wales, Australia
  3. 3Department of Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia
  4. 4Kinghorn Centre for Clinical Genomics, Darlinghurst, New South Wales, Australia
  5. 5St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia
  1. Correspondence to Dr Hooi Ling Teoh, Department of Pediatric Neurology, Sydney Children's Hospital, High Street, Randwick, NSW 2031, Australia; hooiling.teoh{at}health.nsw.gov.au

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The diagnosis of neuromuscular disorders traditionally involved clinical and neurophysiological assessment, pathological evaluation of muscle and/or nerve biopsy and sequential testing of individual genes. Next generation sequencing (NGS) has revolutionised the diagnostic paradigm in genetic disorders, with the capability to capture and sequence genes, the entire exome (1% of the protein coding genome) or the entire genome.1 ,2 While this may overcome the diagnostic odyssey of sequential single gene testing and reduce the need for biopsies, it is important for clinicians to be aware of the challenges and limitations of NGS.3 It is difficult to detect structural DNA differences with whole exome sequencing (WES), including copy number variants such as intragenic deletions or duplications due to variation in depth of coverage, or the number of times a nucleotide is sequenced. While balanced translocations and …

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