Improving the Diagnosis of Neuromuscular Diseases

We now live in a golden period for genetic disease diagnosis where advances in DNA sequencing technology has dramatically accelerated the diagnosis of neuromuscular diseases (NMD), reducing diagnosis time from years to a matter of a few weeks. Rapid diagnosis is critical for families affected by these severe diseases, allowing them to make important decisions about family planning, delaying disease progression, and to decide on therapeutic options.The majority of disease causing mutations are discovered in protein-coding regions (known collectively as the exome), but current exome approaches have a diagnosis rate of just 40%. We aim to increase the diagnosis rate through inspecting regions outside the exome using whole-genome sequencing. In addition, we will use RNA sequencing to gain direct insight into the functional impact of DNA changes on muscle function.

Finally, we will leverage an unprecedented collection of over 60,000 sequenced control samples to improve methods for identifying which of the millions of variants in a patient’s DNA are most likely to cause their disease, and to minimize the risk of false diagnoses. We will apply this approach to a cohort of over 1000 individuals from families with neuromuscular diseases. The identification of novel NMD genes will provide deeper understanding of common disease mechanisms. Future treatment can then be prioritize to target common mechanisms such that it can benefit a larger number of patients.