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Improving molecular diagnosis of distal myopathies by targeted next-generation sequencing
  1. Amandine Sevy1,2,
  2. Mathieu Cerino2,3,
  3. Svetlana Gorokhova2,
  4. Eugénie Dionnet2,
  5. Yves Mathieu2,
  6. Annie Verschueren1,
  7. Jérôme Franques1,
  8. André Maues de Paula2,4,
  9. Dominique Figarella-Branger4,
  10. Arnaud Lagarde2,
  11. Jean Pierre Desvignes2,
  12. Christophe Béroud2,3,
  13. Shahram Attarian1,2,
  14. Nicolas Levy2,3,
  15. Marc Bartoli2,3,
  16. Martin Krahn2,3,
  17. Emmanuelle Campana-Salort1,2,
  18. Jean Pouget1,2
  1. 1APHM, Department of Neurology, Neuromuscular and ALS Reference Center, La Timone University Hospital, Marseille, France
  2. 2Aix Marseille Université, INSERM, GMGF, Marseille, France
  3. 3APHM, Département de Génétique Médicale, Hôpital Timone Enfants, Marseille, France
  4. 4APHM, Department of Anatomopathology, La Timone University Hospital, Marseille, France
  1. Correspondence to Dr Amandine Sevy, Neuromuscular and ALS Reference Center, La Timone University Hospital, Aix-Marseille University, 264 rue Saint-Pierre, Marseille 13385, France; amandine.sevy{at}ap-hm.frEC-S and JP contributed equally to this study.

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Distal myopathies are a heterogeneous group of muscle diseases sharing the clinical pattern of predominant weakness in the feet and/or hands. The classical approach for molecular diagnosis is based on targeted gene-by-gene analysis guided by currently existing combinatorial algorithms.1 Many patients remain undiagnosed. Within the last 5 years, next-generation sequencing (NGS) has emerged as a successful and rapid approach to simultaneously analyse multiple genes in neuromuscular disorders.2 Our objective was to evaluate the efficiency of a targeted NGS approach using a panel of neuromuscular genes on patients with distal myopathies. We first tested its validity in a control group of six index cases (IC) with known molecular diagnosis. Then, we prospectively evaluated this approach by testing a group of 17 IC without molecular diagnosis.

Subjects and methods


We prospectively included 54 patients (37 IC and 17 relatives) with a diagnosis of distal myopathy, followed at the Neuromuscular Diseases and ALS Reference Centre of La Timone Hospital, Marseille, France, between 1989 and 2014. Among these 37 IC previously explored by Sanger sequencing, 20 IC had an identified molecular diagnosis: six IC constituted the control group. The remaining 17 undiagnosed IC constituted the test group. A targeted-NGS approach was used to search mutations in 298 neuromuscular genes in both groups. Samples analysed in this study have been prepared and stored by the Center of Biological Resources, Department of Medical Genetics, La Timone Hospital, Marseille, and used following the ethical recommendations of our institution and according to the Declaration of Helsinki. All included patients gave their written consent prior to …

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethical recommendations of our institution and according to the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.