Advances in the Genetic Testing of Neuromuscular Diseases

Genetic testing in clinical practice commonly involves next-generation sequencing and most testing has been focused on specific sets of genes that are relevant to the clinical presentation (disease specific panels). Testing has typically been performed on DNA isolated from blood leukocytes. Exome sequencing is also available on for clinical testing. Some patients are particularly challenging, with negative genetic testing including (in some cases) whole exome sequencing. For some neuromuscular patients, testing of DNA or RNA isolated from muscle may provide clues that lead to the patient's diagnosis. This article presents cases to illustrate testing algorithms that may establish cases of mosaicism of the proband or parent, mitochondrial DNA mosaicism, genomic rearrangements, or novel genetic diagnoses.