Clinical massively parallel sequencing for the diagnosis of myopathies

Rev Neurol (Paris). Jun-Jul 2015;171(6-7):558-71. doi: 10.1016/j.neurol.2015.02.019. Epub 2015 May 26.


Massively parallel sequencing, otherwise known as high-throughput or next-generation sequencing, is rapidly gaining wide use in clinical practice due to possibility of simultaneous exploration of multiple genomic regions. More than 300 genes have been implicated in neuromuscular disorders, meaning that many genes need to be considered in a differential diagnosis for a patient affected with myopathy. By providing sequencing information for numerous genes at the same time, massively parallel sequencing greatly accelerates the diagnostic processes of myopathies compared to the classical "gene-after-gene" approach by Sanger sequencing. In this review, we describe multiple advantages of this powerful sequencing method for applications in myopathy diagnosis. We also outline recent studies that used this approach to discover new myopathy-causing genes and to diagnose cohorts of patients with muscular disorders. Finally, we highlight the key aspects and limitations of massively parallel sequencing that a neurologist considering this test needs to know in order to interpret the results of the test and to deal with other issues concerning the test.

Keywords: Analyses génétiques; Exome; Genetic testing; Genome; Génome; Génétique médicale; High-throughput DNA sequencing; Maladies musculaires; Massively parallel sequencing; Medical genetics; Muscular diseases; Mutation; Myopathie; Myopathy; Next-generation sequencing; Séquençage de nouvelle génération; Séquençage massif parallèle; Séquençage à haut débit.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Exome / genetics
  • Genome / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Muscular Diseases / diagnosis*
  • Muscular Diseases / genetics*