Research and Diagnostic Validity of Whole Exome Sequencing in Neuromuscular Disease

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Neuromuscular diseases (NMDs) are a broad group of inherited genetic disorders with a total global prevalence exceeding 1 in 3,000. Affecting the muscle and peripheral nervous system, NMDs result in significant disability and despite increased understanding of their molecular basis, the cause is unknown in the majority of patients. In an NCGENES patient cohort, we examined the diagnostic yield of whole exome sequencing (WES) for variants in genes currently associated with NMDs, neuropathies, and myopathies, and we evaluated the literature for known information about these genes. We analyzed the variants from WES in genes not on the current diagnostic lists to search for novel, rare, deleterious variants in possible disease candidate genes and identify patient candidates for further molecular analysis. Based on literature and clinical reports, we also evaluated the construction of the current diagnostic lists, expanding the myopathy and neuropathy lists by over 80 genes each. The lists were curated so that NMD list encompassed all myopathy and neuropathy genes, while the myopathy and neuropathy lists remained as unique as possible. Based on our overall analysis, we constructed a schematic to aid clinicians in deciding when to apply WES for patients with a neuromuscular condition of suspected genetic etiology.

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Title	Date Uploaded	Visibility	Actions
Thesis	2019-05-17	Public	Download
2015_Zhou_1.pdf	2019-05-17	Public	Download
2015_Zhou_2.pdf	2019-05-17	Public	Download