[PS17-3A-1] Molecular Diagnosis of Inherited Neuromuscular Diseases by Targeted Next-Generation Sequencing: Outcomes and Lessons Learned
Inherited Neuromuscular diseases (INMDs) are genetically and clinically heterogeneous diseases, mainly involving spinal motoneurons, neuromuscular junctions, nerves, and muscles. The majority of INMDs are degenerative and rare. An early definitive molecular diagnosis of INMDs is crucial for precise recurrence risk counseling, therapeutic strategies including providing standard of care and approaching the potential available clinical trials, long-term care plans, and accurate prognosis.
With the ever-increasing number of causative genes and clinical heterogeneity, a comprehensive molecular approach with the feasibility to add newly discovered genes for analysis in a cost- and time-effective manner is needed. The recent development of next-generation sequencing (NGS) has accelerated the discovery of novel INMD phenotypes and genotypes. Compared with the traditional one gene at-a-time Sanger sequencing, NGS is a radically different approach to genetic sequencing. NGS allows for a large number of genes to be captured and sequenced in parallel, creating a huge amount of data in a relatively short period of time at much lower cost “per gene.”
In this presentation, we will share our experiences of using target capture/deep sequencing approach to improve the molecular diagnosis of INMDs, and demonstrate the power of NGS in confirming and expanding clinical phenotypes/genotypes of the extremely heterogeneous NMDs.
We would stress the importance of accurate clinical examination, electrophysiological, and histopathological results, for interpretation of NGS, with many diagnoses requiring follow-up review and ancillary investigations of multiple systems, and uncovering familial aggregation.
With the ever-increasing number of causative genes and clinical heterogeneity, a comprehensive molecular approach with the feasibility to add newly discovered genes for analysis in a cost- and time-effective manner is needed. The recent development of next-generation sequencing (NGS) has accelerated the discovery of novel INMD phenotypes and genotypes. Compared with the traditional one gene at-a-time Sanger sequencing, NGS is a radically different approach to genetic sequencing. NGS allows for a large number of genes to be captured and sequenced in parallel, creating a huge amount of data in a relatively short period of time at much lower cost “per gene.”
In this presentation, we will share our experiences of using target capture/deep sequencing approach to improve the molecular diagnosis of INMDs, and demonstrate the power of NGS in confirming and expanding clinical phenotypes/genotypes of the extremely heterogeneous NMDs.
We would stress the importance of accurate clinical examination, electrophysiological, and histopathological results, for interpretation of NGS, with many diagnoses requiring follow-up review and ancillary investigations of multiple systems, and uncovering familial aggregation.