2 locus. It is quite interesting that both studies revealed the importance of 7q11.23 as an ASD locus. click here While deletions of this region cause Williams syndrome, a multiple congenital anomaly syndrome with hypersociable behaviors, duplications of the same region cause ASDs. The opposing social phenotypes of 7p11.23 deletions and duplications provide a fascinating basis for studies in animal models to pinpoint the genes and neurons mediating these phenotypes. Within the genomic region, CLIP2, LIMK1, GTF2i, and STX1A have been proposed as potential culprit

genes, but the exact underlying pathomechanisms are far from being understood. While the high heritability of autism is well established, the exact underlying causes and mutations are identifiable only in a minority of patients. Using current clinical DNA arrays, relevant de novo genomic imbalances can be identified in 7%–20% of individuals with autism of unknown cause. As expected, the yield is higher in those

individuals with “syndromic” autism. Known single-gene disorders account for another 5%–7% of cases, with fragile X syndrome being the most common (1%–3% of cases), followed by PTEN macrocephaly syndrome, tuberous sclerosis complex, Selleck U0126 and Rett syndrome (each accounting for approximately 1% of children diagnosed with autism) ( Miles, 2011). Timothy syndrome, Joubert syndrome, SHANK3 mutations, NRXN1 mutations, and a handful of other genes account for rare cases. There remain large cohorts of patients that have to be screened for the incidence of respective

point mutations and their contribution to the overall number Chloramphenicol acetyltransferase of autism cases. Lastly, several metabolic conditions have been associated with ASDs, including mitochondrial disorders, phenylketonuria, adenylosuccinate lyase deficiency, creatine deficiency, and some disorders of sterol biosynthesis. In total, known metabolic disorders may account for approximately 5% of cases of ASDs. This leaves us with at least 70% of cases, for which the genetic cause of ASDs cannot yet be identified ( Figure 1). The percentage is even higher for the nonsyndromic cases of ASDs. One would have hoped that the type of detailed analysis of large ASD cohorts using very high-resolution arrays as those used in the Sanders and Levy studies would have yielded a high number of identifiable mutations, yet the results are humbling. There is no remarkable increase in pickup rate of CNVs, despite much increased density when compared to previous studies, pointing to the limitations of array analysis and the contributions of de novo and rare inherited CNVs to the etiology of ASDs overall.