Multiple rare variants in the etiology of autism spectrum disorders.
Recent studies in autism spectrum disorders (ASDs) support an important role for multiple rare variants in these conditions. This is a clinically important finding, as, with the demonstration that a significant proportion of ASDs are the result of rare, etiological genetic variants, it becomes possible to make use of genetic testing to supplement behavioral analyses for an earlier diagnosis. As it appears that earlier interventions in ASDs will produce better outcomes, the development of genetic testing to augment behaviorally based evaluations in ASDs holds promise for improved treatment. Furthermore, these rare variants involve synaptic and neuronal genes that implicate specific pathways, cells, and subcellular compartments in ASDs, which in turn will suggest novel therapeutic approaches in ASDs. Of particular recent interest are the synaptic cell adhesion and associated molecules, including neurexin 1, neuroligin 3 and 4, and SHANK3, which implicate glutamatergic synapse abnormalities in ASDs. In the current review we will overview the evidence for a genetic etiology for ASDs, and summarize recent genetic findings in these disorders.
Laboratory of Molecular Neuropsychiatry, Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. joseph.buxbaum@mssm.edu
Joseph D
JD
Buxbaum
D001321:Autistic Disorder / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D009154:Mutation / Q000235:genetics*