As yet, however, only rare de novo and inherited variants are soundly established genetic risk factors for ASD, and thus far these only account for a small proportion of the total genetic risk. Autism is a possible manifestation of single-gene disorders, such as those due to mutations in FMR1, TSC1, TSC2, MECP2 and PTEN. Some chromosomal rearrangements appear causal, with the most common being maternal duplication of 15q11–q13. Mutations of high penetrance for ASD have been identified in synaptic genes, including NLGN3, NLGN4X and SHANK3 (10,11). Rare deletion CNVs of SHANK3 and the surrounding 22q13.33 region have also been found in individuals with an ASD. In this regard, genome-wide microarray studies have implicated a substantial number of other individually rare submicroscopic CNV loci, including hemizygous deletions and duplications of 16p11.2, NRXN1 and PTCHD1 (12–18).
