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Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders
  1. Jong Hee Chae1,
  2. Valeria Vasta2,
  3. Anna Cho3,
  4. Byung Chan Lim1,
  5. Qing Zhang2,
  6. So Hee Eun4,
  7. Si Houn Hahn2,5
  1. 1Division of Pediatric Neurology, Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
  2. 2Seattle Children's Research Institute, Seattle, Washington, USA
  3. 3Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
  4. 4Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
  5. 5Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA
  1. Correspondence to Dr Si Houn Hahn, Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA; sihahn{at}


Background Neuromuscular disorders are a clinically, pathologically, and genetically heterogeneous group. Even for the experienced clinician, an accurate diagnosis is often challenging due to the complexity of these disorders. Here, we investigated the utility of next generation sequencing (NGS) in early diagnostic algorithms to improve the diagnosis for patients currently lacking precise molecular characterisation, particularly for hereditary myopathies.

Methods 43 patients presenting with early onset neuromuscular disorders from unknown genetic origin were tested by NGS for 579 nuclear genes associated with myopathy.

Results In 21 of the 43 patients, we identified the definite genetic causes (48.8%). Additionally, likely pathogenic variants were identified in seven cases and variants of uncertain significance (VUS) were suspected in four cases. In total, 19 novel and 15 known pathogenic variants in 17 genes were identified in 32 patients. Collagen VI related myopathy was the most prevalent type in our cohort. The utility of NGS was highlighted in three cases with congenital myasthenia syndrome, as early diagnosis is important for effective treatment.

Conclusions A targeted NGS can offer cost effective, safe and fairly rapid turnaround time, which can improve quality of care for patients with early onset myopathies and muscular dystrophies; in particular, collagen VI related myopathy and congenital myasthenia syndromes. Nevertheless, a substantial number of patients remained without molecular diagnosis in our cohort. This may be due to the intrinsic limitation of detection for some types of mutations by NGS or to the fact that other causative genes for neuromuscular disorders are yet to be identified.

  • Peripheral nerve disease
  • Motor neurone disease
  • Molecular genetics
  • Muscle disease
  • Neuromuscular disease

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