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Genetic testing in motor neurone disease
  1. Thanuja Dharmadasa1,
  2. Jakub Scaber1,
  3. Evan Edmond1,
  4. Rachael Marsden2,
  5. Alexander Thompson1,2,
  6. Kevin Talbot1,
  7. Martin R Turner1
  1. 1 Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
  2. 2 Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  1. Correspondence to Professor Martin R Turner, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, Oxfordshire, UK; martin.turner{at}


A minority (10%–15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological variants in a single identifiable gene. With the emergence of new therapies targeting specific genetic subtypes of ALS, there is an increasing role for routine genetic testing for all those with a definite diagnosis. However, potential harm to both affected individuals and particularly to asymptomatic relatives can arise from the indiscriminate use of genetic screening, not least because of uncertainties around incomplete penetrance and variants of unknown significance. The most common hereditary cause of ALS, an intronic hexanucleotide repeat expansion in C9ORF72, may be associated with frontotemporal dementia independently within the same pedigree. The boundary of what constitutes a possible family history of MND has therefore extended to include dementia and associated psychiatric presentations. Notwithstanding the important role of clinical genetics specialists, all neurologists need a basic understanding of the current place of genetic testing in MND, which holds lessons for other neurological disorders.

  • ALS
  • genetics
  • motor neurone disease
  • neurogenetics
  • clinical neurology

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  • Contributors TD drafted the manuscript and figures. JS, EE, RM, AT, KT edited the manuscript. MRT conceived and edited the manuscript.

  • Funding TD is funded by a NHMRC CJ Martin Post-Doctoral Fellowship. EE is funded by the Association of British Neurologists and Dunhill Medical Trust Fellowship. AT is funded by the Medical Research Council and Motor Neurone Disease Association Lady Edith Wolfson Clinician Scientist Fellowship. MRT receives funding support from the Motor Neuron Disease Association.

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  • Competing interests None declared.

  • Provenance and peer review Commissioned and externally reviewed by Huw Morris, London, UK.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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