Delineation of molecular basis of autism using array CGH

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Autism is a complex developmental disability that typically appears during the first three years of life and is the result of a neurological disorder that affects the normal functioning of the brain, impacting development in the areas of social interaction and communication skills. Presumably, genetic background contributes to autism. Yet, only 10% of patients exhibit definitive genetic abnormalities. We designed a custom array with 60000 probes. Probes were densely allocated at genes on X chromosome, genes of which mutations are known to cause multiple malformation syndromes with developmental delay(i. e. Cornelia de Lange syndrome, Rubinstein-Taybi syndrome), and genes already known to be related with autism(NLGN3, NGLN4, NRXN1, SHANK3, CNTNAP2, PCDH10, CNTN3, NHE9, NHE6, DIA1, and A2BP1) and their homologous/upstream/downstream genes.We have identified two critical cases : One patient who had a duplication of 5.4MB at 6q14, 2-15 including the GABA receptor GABRB3 ; the other patient had a deletion of 6.6MB at 2p16.3 including NRXN1. NRXN forms a complex with NLGN on the post synaptic membrane and plays a critical role on neural transmission mediated through GABA receptors and glutamine receptors. We suggest that duplication of GABRB3 and deletion of NRXN1 contributes to autism.