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Research paper
Two recurrent mutations are associated with GNE myopathy in the North of Britain
  1. Amina Chaouch1,
  2. Kathryn M Brennan1,2,
  3. Judith Hudson1,
  4. Cheryl Longman3,
  5. John McConville4,
  6. Patrick J Morrison4,
  7. Maria E Farrugia2,
  8. Richard Petty2,
  9. Willie Stewart2,
  10. Fiona Norwood5,
  11. Rita Horvath1,
  12. Patrick F Chinnery1,
  13. Donald Costigan6,
  14. John Winer7,
  15. Tuomo Polvikoski1,
  16. Estelle Healy8,
  17. Anna Sarkozy1,
  18. Teresinha Evangelista1,
  19. Oksana Pogoryelova1,
  20. Michelle Eagle1,
  21. Kate Bushby1,
  22. Volker Straub1,
  23. Hanns Lochmüller1
  1. 1Institute of Genetic Medicine, MRC Centre for Neuromuscular Disease, Newcastle University, Newcastle upon Tyne, UK
  2. 2Institute of Neurological Sciences, Glasgow, UK
  3. 3West of Scotland Regional Genetics Service, Southern General Hospital, Glasgow, UK
  4. 4Belfast City Hospital, Belfast, UK
  5. 5Department of Neurology, King's College Hospital, London, UK
  6. 6National Institute for Neurology and Neurosurgery, Beaumont Hospital, Dublin, Ireland
  7. 7Birmingham Muscle and Nerve Centre, Queen Elizabeth Hospital, Birmingham, UK
  8. 8Institute of Pathology, Royal Victoria Hospital, Belfast, UK
  1. Correspondence to Professor Hanns Lochmüller, Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK; hanns.lochmuller{at}


Objective GNE myopathy is a rare recessive myopathy associated with inclusion bodies on muscle biopsy. The clinical phenotype is associated with distal muscle weakness with quadriceps sparing. Most of the current information on GNE myopathy has been obtained through studies of Jewish and Japanese patient cohorts carrying founder mutations in the GNE gene. However, little is known about GNE myopathy in Europe where the prevalence is thought to be very low.

Methods Patients were referred through the National Specialist Commissioning Team service for limb-girdle muscular dystrophies at Newcastle (UK). All patients harbouring mutations in the GNE gene were recruited for our study. Detailed clinical and genetic data as well as muscle MRIs and muscle biopsies were reviewed.

Results We identified 26 patients harbouring mutations in the GNE gene. Two previously reported mutations (c.1985C>T, p.Ala662Val and c.1225G>T, p.Asp409Tyr) were prevalent in the Scottish, Northern Irish and Northern English populations; with 90% of these patients carrying at least one of the two mutations. Clinically, we confirmed the homogenous pattern of selective quadriceps sparing but noted additional features like asymmetry of weakness at disease onset.

Conclusions GNE myopathy is an important diagnosis to consider in patients presenting with distal leg muscle weakness. We report, for the first time, two common mutations in the north of Britain and highlight the broader spectrum of clinical phenotypes. We also propose that the prevalence of GNE myopathy may be underestimated due to the frequent absence of rimmed vacuoles in the muscle biopsy.


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