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. 2009 Oct;17(10):1347-53.
doi: 10.1038/ejhg.2009.47. Epub 2009 Apr 22.

Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection

Nuala H Sykes  1 , Claudio Toma, Natalie Wilson, Emanuela V Volpi, Inês Sousa, Alistair T Pagnamenta, Raffaella Tancredi, Agatino Battaglia, Elena Maestrini, Anthony J Bailey, Anthony P Monaco; International Molecular Genetic Study of Autism Consortium (IMGSAC)
Affiliations

Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection

Nuala H Sykes et al. Eur J Hum Genet. 2009 Oct.

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.

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Figures

Figure 1
Figure 1
Copy number analysis using MLPA on the region chr22q12.2-q13.33 in 168 autistic probands from IMGSAC multiplex families and Italian singleton families. The thresholds for gains and losses are marked as 1.3 and 0.7, respectively. The positive control sample clearly shows the loss of SHANK3, ACR and RABL2B. Graph not to scale. For a complete list of the probes and their positions see MRC-Holland probe mix P188 lot 0407, 0906.
Figure 2
Figure 2
Positions of SNPs, fosmids and MLPA probes within SHANK3 (UCSC May 2004, NCBI Build 35). Exons annotated as those in the study by Durand et al.
See this image and copyright information in PMC

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