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Lessons and pitfalls of whole genome sequencing
  1. Christopher J Record,
  2. Mary M Reilly
  1. Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
  1. Correspondence to Professor Mary M Reilly, Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; m.reilly{at}ucl.ac.uk; Dr Christopher J Record, Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK; chris.record{at}ucl.ac.uk

Abstract

Whole-genome sequencing (WGS) has recently become the first-line genetic investigation for many suspected genetic neurological disorders. While its diagnostic capabilities are innumerable, as with any test, it has its limitations. Clinicians should be aware of where WGS is extremely reliable (detecting single-nucleotide variants), where its reliability is much improved (detecting copy number variants and small repeat expansions) and where it may miss/misinterpret a variant (large repeat expansions, balanced structural variants or low heteroplasmy mitochondrial DNA variants). Bioinformatic technology and virtual gene panels are constantly evolving, and it is important to know what genes and what types of variant are being tested; the current National Health Service Genomic Medicine Service WGS offers more than early iterations of the 100 000 Genomes Project analysis. Close communication between clinician and laboratory, ideally through a multidisciplinary team meeting, is encouraged where there is diagnostic uncertainty.

  • GENETICS
  • NEUROPATHY
  • NEUROGENETICS
  • HMSN (CHARCOT-MARIE-TOOTH)

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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Footnotes

  • Contributors CJR analysed the data and wrote the manuscript. MMR conceptualised the study and provided senior critical review and revisions.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned. Externally peer reviewed by Rhys Thomas, Newcastle-upon-Tyne, UK.

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