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The Applications and Challenges of Next-Generation Sequencing in Diagnosing Neuromuscular Disorders

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Next Generation Sequencing Based Clinical Molecular Diagnosis of Human Genetic Disorders

Abstract

Inherited neuromuscular disorders (NMDs) form a group of highly heterogeneous diseases with a relatively high incidence of 1 in 3000. NMDs affect the peripheral nervous and muscular systems, resulting in gross motor disability. Disease subtype diagnosis is complicated by the high clinical and genetic heterogeneities of the disease and consequently more than 50% of the cases remain molecularly uncharacterized. Traditional gene-by-gene approach is quite exhaustive and after a few negative tests the quest for diagnosis is often given up without establishing diagnosis. However in the recent years, the clinical applications of next-generation sequencing (NGS)-based comprehensive approach such as multi-gene panels, and exome sequencing have allowed for rapid diagnosis. Additionally, its applications in research settings have allowed for identification of new disease-causing genes and variants which translated into an improved clinical diagnostic yield. Here, we discuss the application of NGS technology in NMDs as a diagnostic and research tool. We conclude that such an application will tremendously broaden our knowledge of NMDs; the outcome of which includes rapid and accurate diagnosis that would result in an earlier and more effective intervention.

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Authors and Affiliations

  1. Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Lijun Wang, Xinjian Wang, Ammar Husami, Kejian Zhang & C. Alexander Valencia

  2. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA

    Arunkanth Ankala & Hamoud Al Khallaf

  3. Keck Graduate Institute, Claremont, CA, USA

    Mikhail Martchenko

  4. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Biao Dong

  5. Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Ave. R1-1028, MLC 7016, Cincinnati, OH, 45229, USA

    Kejian Zhang & C. Alexander Valencia

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  1. Lijun Wang
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  2. Arunkanth Ankala
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  9. C. Alexander Valencia
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Correspondence to C. Alexander Valencia .

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  1. Molecular Diagnostic Laboratory, Baylor College of Medicine, Houston, Texas, USA

    Lee-Jun C. Wong

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Wang, L. et al. (2017). The Applications and Challenges of Next-Generation Sequencing in Diagnosing Neuromuscular Disorders. In: Wong, LJ. (eds) Next Generation Sequencing Based Clinical Molecular Diagnosis of Human Genetic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-56418-0_10

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