Diagnostic use of Massively Parallel Sequencing in Neuromuscular Diseases: Towards an Integrated Diagnosis.

Abstract

Massively parallel sequencing is revolutionizing the genetic testing in diagnosis laboratories, replacing gene-by-gene investigations with a “gene panel” strategy. This new approach is particularly promising for the diagnosis of neuromuscular disorders affecting children as well as adults, which is constrained by strong clinical and genetic heterogeneity. While it leads to a strong improvement in molecular diagnosis, this new approach is dramatically changing the whole diagnosis process, establishing new decision trees and requiring integrated strategies between clinicians and laboratories. To have an overview of the implementation and benefit of these novel sequencing strategies for the diagnosis of neuromuscular disorders, we surveyed the current literature on the application of targeted genes panel sequencing, exome sequencing and genome sequencing. We highlight advantages and disadvantages of these different strategies in a diagnosis setting, discuss about unresolved cases, and point potential validation approaches and outcomes of massively parallel sequencing. It appears important to integrate such novel strategies with clinical, histopathological and imaging investigations, for a faster and more accurate diagnosis and patient care, and to foster research projects and clinical trials.