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Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders

Title
Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders
Authors
Chae J.H.Vasta V.Cho A.Lim B.C.Zhang Q.Eun S.H.Hahn S.H.
Ewha Authors
조안나
SCOPUS Author ID
조안나scopus
Issue Date
2015
Journal Title
Journal of Medical Genetics
ISSN
0022-2593JCR Link
Citation
vol. 52, no. 3, pp. 208 - 216
Publisher
BMJ Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.1136/jmedgenet-2014-102819
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의과대학 > 의학과 > Journal papers
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