title: Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection.
abstract: SHANK3 is located on chromosome 22q13.3 and encodes a scaffold protein that is found in excitatory synapses opposite the pre-synaptic active zone. SHANK3 is a binding partner of neuroligins, some of whose genes contain mutations in a small subset of individuals with autism. In individuals with autism spectrum disorders (ASDs), several studies have found SHANK3 to be disrupted by deletions ranging from hundreds of kilobases to megabases, suggesting that 1% of individuals with ASDs may have these chromosomal aberrations. To further analyse the involvement of SHANK3 in ASD, we screened the International Molecular Genetic Study of Autism Consortium (IMGSAC) multiplex family sample, 330 families, for SNP association and copy number variants (CNVs) in SHANK3. A collection of 76 IMGSAC Italian probands from singleton families was also examined by multiplex ligation-dependent probe amplification for CNVs. No CNVs or SNP associations were found within the sample set, although sequencing of the gene was not performed. Our data suggest that SHANK3 deletions may be limited to lower functioning individuals with autism.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Nuala H
authors.initials: NH
authors.lastname: Sykes
authors.forename: Claudio
authors.initials: C
authors.lastname: Toma
authors.forename: Natalie
authors.initials: N
authors.lastname: Wilson
authors.forename: Emanuela V
authors.initials: EV
authors.lastname: Volpi
authors.forename: Inês
authors.initials: I
authors.lastname: Sousa
authors.forename: Alistair T
authors.initials: AT
authors.lastname: Pagnamenta
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tancredi
authors.forename: Agatino
authors.initials: A
authors.lastname: Battaglia
authors.forename: Elena
authors.initials: E
authors.lastname: Maestrini
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bailey
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002352:Carrier Proteins; D002869:Chromosome Aberrations; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D008297:Male; D008957:Models, Genetic; D009419:Nerve Tissue Proteins; D013569:Synapses / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human