[P3-134] Targeted Next Generation Sequencing in Undiagnosed Early-onset Neuromuscular Disorders
Neuromuscular disorders are clinically, pathologically, and genetically heterogeneous groups of disorders. Particularly during infancy and childhood, the clinical presentation shares similar features such as hypotonia, weakness, and motor developmental delay, which make it difficult to reach a specific diagnosis even for the experienced clinicians. An accurate genetic diagnosis has often been challenging due to the heterogeneity and complexity of these groups of disorders. The advent of next generation sequencing (NGS) technologies have started a new era of molecular genetic diagnosis in neuromuscular disorders. It is an effective diagnostic tool for the parallel investigation of a large number of genes and has been increasingly used in the recent clinical and research fields. We applied an NGS-based platform to the diagnostic workflow in the genetic characterization of patients with early onset neuromuscular disorders. We have set up the targeted sequencing panels cover 434 causative genes known for hereditary neuromuscular disorders. Total 176 cases with undiagnosed early-onset neuromuscular disorders were analyzed and one third of them (n = 53) were genetically confirmed up to date. A further 64 cases had unproven candidate variants as yet. Pathogenic variants were found in 39 of 434 genes. Our study illustrates the clinical utility of targeted NGS as a powerful diagnostic tool in early-onset hereditary neuromuscular disorders. It can be advantageous as a first-tier test in view of less-invasive clinical approach, diagnosis speed, and cost-effectiveness.