Whole-exome sequencing in neurologic practice: Reducing the diagnostic odyssey

The current issue of Neurology® Genetics emphasizes the unparalleled role of next-generation sequencing (NGS) in defining an expanding spectrum of genetic neurologic disorders. Clinically, NGS encompasses the use of large gene panels, whole-exome sequencing (WES), or whole-genome sequencing (WGS). The impact of NGS technology is twofold. First, researchers have discovered novel genes as the cause of neurologic disorders. This research includes the efforts of Martikainen et al.(1) to define further the phenotype of a previously reported SNCA mutation that is associated with autosomal dominant Parkinson disease. Second and more common is the connection of novel phenotypes with previously described genes. Several articles in the current issue highlight the role of NGS in this effort. For example, Schottman et al.(2) identified REEP1 mutations as the cause of a severe axonal neuropathy with a spinal muscular atrophy with respiratory distress (SMARD) phenotype. This gene was previously associated with a hereditary spastic paraplegia phenotype. Similarly, Shieh et al.(3) expand the phenotype associated with mutations in L1CAM to a neuronal migration phenotype.