Vol 11, N°1 Child and Adolescent Psychiatry
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Autism spectrum disorders utism, also referred to as autistic disorder (des- ignated  as  OMIM  #209850,  by  Online  Mendelian Inheritance in Man, an online database of human genes and genetic phenotypes), is a developmental neuropsy- chiatric disorder that was first described in 1943 by Dr Leo   Kanner.1   DSM-IV   (Diagnostic   and   Statistical Manual, 4th Edition,American Psychiatric Association), or similar criteria are used for diagnosis of autism and other disorders in this spectrum, referred to as the per- vasive developmental disorders (PDD). DSM-IV crite- ria for autism include onset by age 3, impairments in social interaction and in social communication, as well as repetitive and stereotypic patterns of behaviors or restricted  interests. Asperger  syndrome  represents  a higher-functioning form of ASD. Pervasive developmen- tal disorder-not otherwise specified (PDD-NOS) also involves deficits in all three domains (social interaction, social communication, characteristic behaviors/inter- ests), but the deficits do not reach threshold criteria for an autism diagnosis. In this review, Asperger syndrome, T r a n s l a t i o n a l   r e s e a r c h A Copyright © 2009 LLS SAS.  All rights reserved www.dialogues-cns.org Multiple rare variants in the etiology of autism spectrum disorders Joseph D. Buxbaum, PhD Keywords:  pervasive developmental disorder; autism spectrum disorder; gene- tics; association; susceptibility locus Author   affiliations:    Laboratory   of   Molecular   Neuropsychiatry,   Seaver Autism  Center  for  Research  and  Treatment,  Departments  of  Psychiatry, Neuroscience, and Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA Address  for  correspondence:  Joseph  D.  Buxbaum,  Department  of  Psychiatry, One Gustave L. Levy Place, Box 1668, New York, NY 10029, USA (e-mail: joseph.buxbaum@mssm.edu) Recent studies in autism spectrum disorders (ASDs) sup- port 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 sup- plement 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 com- partments in ASDs, which in turn will suggest novel ther- apeutic approaches in ASDs. Of particular recent inter- est   are   the   synaptic   cell   adhesion   and   associated molecules, including neurexin 1, neuroligin 3 and 4, and SHANK3, which implicate glutamatergic synapse abnor- malities in ASDs. In the current review we will overview the evidence for a genetic etiology for ASDs, and sum- marize recent genetic findings in these disorders. © 2009, LLS SAS Dialogues Clin Neurosci.  2009;11:35-43.