58-60 A recent study suggests that mutations in NGLN4Y might also result in an ASD.34 Disruption of Nlgn4x in mice leads to deficits in reciprocal social interactions and communication.61 It has been reported that introducing the R451C mutation in murine NlgnS was reported to result in impaired social interactions with an increase in inhibitory synaptic transmission62; however.these behavioral deficits were not seen in an independent study.63 CNTNAP2 Cortical dysplasia-focal epilepsy syndrome

was first described in 2006 in Amish children displaying cortical dysplasia, focal epilepsy, relative macrocephaly, diminished deep-tendon reflexes, Inhibitors,research,lifescience,medical language regression, MR, and ASD.64 The disorder is recessive and caused by mutations in the CNTNAP2 gene, which codes for contactin-asso ciated protein-like 2 (CASPR2) that is involved in localization

of voltage -gated potassium channels (K(v)l .1) at the juxtaparanodes of the nodes of Ran Inhibitors,research,lifescience,medical vier. Three recent studies assessed this gene in ASDs. First, following up on a linkage result of a language-related autism QTL, it was suggested Inhibitors,research,lifescience,medical that common variants of CNTNAP2 may increase risk for ASDs in male-only families, and it was shown that CNTNAP2 is expressed in language- and cognition-related circuits.65 This finding was also observed in a related study using overlapping AG RE families.66 Finally, rare Inhibitors,research,lifescience,medical variants of the CNTNAP2, and particularly the I869T variant, also show some association with ASD.67 PTEN Our own studies on PTEN mutations in ASD can serve to highlight the clinical value of identifying mutations in ASD.68 Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease, as well as ASDs (reviewed in ref 68). We surveyed head circumference information from hundreds Inhibitors,research,lifescience,medical of subjects with ASD and sequenced the PTEN gene in 88 individuals showing macrocephaly (defined as a head

circumference ≥2 standard deviations above the mean). We identified a de novo missense mutation (D326N) in a highly conserved amino why acid in a 5-year-old boy with autism, MR, language delay, and extreme macrocephaly (+9.6 SD).The identification of this mutation can give important information to the family with regard to recurrence risk, and also improve the care of the affected boy because an appropriate selleck chemicals surveillance strategy for P’FfiW-mutation-related conditions can be initiated. Etiological yield in ASDs The importance of evaluating ASD-associated syndromes in the clinical context needs to be emphasized. A recent study used a three-tiered neurogenetic evaluation scheme to evaluate 32 patients with a behavioral diagnosis of an ASD.