title: From de novo mutations to personalized therapeutic interventions in autism.
abstract: The high heritability, early age at onset, and reproductive disadvantages of autism spectrum disorders (ASDs) are consistent with an etiology composed of dominant-acting de novo (spontaneous) mutations. Mutation detection by microarray analysis and DNA sequencing has confirmed that de novo copy-number variants or point mutations in protein-coding regions of genes contribute to risk, and some of the underlying causal variants and genes have been identified. As our understanding of autism genes develops, the spectrum of autism is breaking up into quanta of many different genetic disorders. Given the diversity of etiologies and underlying biochemical pathways, personalized therapy for ASDs is logical, and clinical genetic testing is a prerequisite.
authors.affiliation: Beyster Center for Genomics of Psychiatric Diseases.
authors.forename: William M
authors.initials: WM
authors.lastname: Brandler
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
mesh_terms: D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000628:therapy; D056915:DNA Copy Number Variations; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods*; D017422:Sequence Analysis, DNA
keywords: Rett syndrome; autism spectrum disorder; clinical trials; copy-number variation; fragile X syndrome; genomics; metabolic disorders; mouse models; whole-genome sequencing