Purpose of review: Neuromuscular diseases are clinically and genetically heterogeneous and probably contain the greatest proportion of causative Mendelian defects than any other group of conditions. These disorders affect muscle and/or nerves with neonatal, childhood or adulthood onset, with significant disability and early mortality. Along with heterogeneity, unidentified and often very large genes require complementary and comprehensive methods in routine molecular diagnosis. Inevitably, this leads to increased diagnostic delays and challenges in the interpretation of genetic variants.
Recent findings: The application of next-generation sequencing, as a research and diagnostic strategy, has made significant progress into solving many of these problems. The analysis of these data is by no means simple, and the clinical input is essential to interpret results.
Summary: In this review, we describe using examples the recent advances in the genetic diagnosis of neuromuscular disorders, in research and clinical practice and the latest developments that are underway in next-generation sequencing. We also discuss the latest collaborative initiatives such as the Genomics England (Department of Health, UK) genome sequencing project that combine rare disease clinical phenotyping with genomics, with the aim of defining the vast majority of rare disease genes in patients as well as modifying risks and pharmacogenomics factors.