Most recently, whole exome—consisting of all protein coding regions in the genome—sequencing (WES) has been applied to identify the genes involved in autism. This approach was inspired by the successful introduction of WES to identify genetic causes of neurodevelopmental disorders [Veltman and Brunner, 2012]. After a proof of principle study comparing the exomes of a pilot cohort of 10 ID patients with those of the parents, likely causative mutations were identified in six cases [Vissers et al., 2010]. Subsequent studies using the same so called trio approach in larger cohorts of up to 250 patients showed a diagnostic yield in the range of up to 50% [de Ligt et al., 2012; Rauch et al., 2012; Yang et al., 2013]. In autism, it was discovered that de novo potentially deleterious (e.g., amino acid changing) SNPs were significantly more prevalent in patients than in unaffected relatives or controls. Based on the trio and quartet approach, consisting of patient, parents, and unaffected sibling, the most frequently mutated genes identified so far include CDH8, SCN2A, DYRK1A, and CTNNB1 [O’Roak et al., 2012a; Krumm et
