Chapter 6 - Next Generation Sequencing in Neurology and Psychiatry

Abstract

The introduction of next generation sequencing (NGS) technologies has paved a new way to the identification of novel variants, helping to unravel the genetic complexity of various disorders of the nervous system. In this chapter the state-of-the-art, recent findings, methodological problems, and future directions of whole-genome/exome analysis of these conditions are summarized. Moreover, the authors evaluate the impact of NGS in neurology and psychiatry as well as its consequences leading to improved patient care. NGS offers novel, attractive options for the genetic diagnosis of many common and rare disorders of the nervous system presenting with various neurological and mental symptoms. The advent of NGS is revolutionizing genetic testing in neuropsychiatry, enabling rapid identification and validation of rare and disruptive variants that can contribute to phenotypic outcomes of extreme levels of heterogeneity. Whole-exome sequencing (WES) may be the only tool to establish a molecular diagnosis for patients with nonspecific phenotypes such as autism, schizophrenia, epilepsies, peripheral neuropathy, neurodegenerative disorders with pyramidal or extrapyramidal syndrome or ataxia of unknown etiology, early-onset familial dementia, and dystonia. NGS has already been successfully used to uncover missing heritability in autism and mental retardation, with the clinical utility of WES shown to be up to ∼30%. NGS testing may lead to better understanding of pathophysiology and predisposition to nervous system disorders and/or improve the approach to pharmacotherapy and pharmacogenetics.