Advances in genetic diagnosis of neurological disorders

Neurogenetics has developed enormously in recent years, and the genetic basis of human disorders is being unravelled rapidly. Many neurological disorders are Mendelian disorders, caused by mutations in genes involved in normal function of the brain, spinal cord, peripheral nerves or muscles. Due to high costs and time‐consuming procedures, genetic tests have normally been performed late in the diagnostic process, when clinical examination and other tests have indicated a specific gene as the likely disease cause. Many neurological phenotypes are genetically very heterogeneous, and testing of all possible disease genes has been impossible. As a result, many patients with genetic neurological disorders have remained without a specific diagnosis, even when the disease is caused by mutations in known disease genes. Recent technological advances, in particular next‐generation DNA sequencing techniques, have resulted in rapid identification of genes involved in Mendelian disorders and provided new possibilities for diagnostic genetic testing. The development of methods for coupling targeted capture and massively parallel DNA sequencing has made it possible to examine a large number of genes in a single reaction. Diagnostic genetic testing can today be performed by the use of gene panels and exome sequencing. This allows a more precise diagnosis of many neurological disorders, and genetic testing should now be considered earlier in the diagnostic procedure.