1. Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, Sonnenblick LI, Alvarez Retuerto AI, Imielinski M, Hadley D, Bradfield JP, Kim C, Gidaya NB, Lindquist I, Hutman T, Sigman M, Kustanovich V, Lajonchere CM, Singleton A, Kim J, Wassink TH, McMahon WM, Owley T, Sweeney JA, Coon H, Nurnberger JI, Li M, Cantor RM, Minshew NJ, Sutcliffe JS, Cook EH, Dawson G, Buxbaum JD, Grant SF, Schellenberg GD, Geschwind DH, Hakonarson H. {{Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes}}. {PLoS Genet};2009 (Jun);5(6):e1000536.
2. Neves-Pereira M, Muller B, Massie D, Williams JH, O’Brien PC, Hughes A, Shen SB, St Clair D, Miedzybrodzka Z. {{Deregulation of EIF4E: a novel mechanism for autism}}. {J Med Genet};2009 (Jun 25)
Autism is a common childhood onset neurodevelopmental disorder, characterized by severe and sustained impairment of social interaction and social communication, as well as a markedly restricted repertoire of activities and interests. Its aetiology is multifactorial with a strong genetic basis. EIF4E is the rate-limiting component of eukaryotic translation initiation, and plays a key role in learning and memory through its control of translation within the synapse. EIF4E mediated translation is the final common process modulated by the mTOR, PTEN and Fragile X mental retardation protein (FMRP) pathways which are implicated in autism. Linkage of autism to the EIF4E region on chromosome 4q has been found in genome wide linkage studies. Here we present evidence that directly implicates EIF4E in autism. In a boy with classic autism we observed a de novo chromosome translocation between 4q and 5q and mapped the breakpoint site to within a proposed alternative transcript of EIF4E. We then screened for mutations 120 autism families. We found two unrelated families where in each case both autistic siblings and one of the parents harboured the same single nucleotide insertion at position -25 in the basal element of the EIF4E promoter. Electrophoretic mobility shift assays and reporter gene studies show that this mutation enhances binding of a nuclear factor and EIF4E promoter activity. These observations implicate EIF4E, and more specifically control of EIF4E activity, directly in autism. Our findings raise the exciting possibility that pharmacological manipulation of EIF4E may provide therapeutic benefit for those with autism caused by disturbance of the converging pathways controlling EIF4E activity.
3. Ruta L, Mugno D, D’Arrigo VG, Vitiello B, Mazzone L. {{Obsessive-compulsive traits in children and adolescents with Asperger syndrome}}. {Eur Child Adolesc Psychiatry};2009 (Jun 26)
