In summary, our data indicate that mutations at the PTCHD1 locus are highly penetrant and strongly associated with ASD (including BAP) and ID in ~1.1% and ~1.3% of the individuals analyzed, respectively (based on probands for whom comprehensive mutation screening, for both CNVs and sequence variants, has been performed (4 out of 353 ASD, and 3 out of 225 ID). Overall, our finding are reminiscent of genetic findings for several other X chromosome genes, including NLGN4 (7,8) and IL1RAPL1 (9,10,34), in that mutations can apparently cause either ASD or ID (or both), and thus PTCHD1 may be a gene for both. IL1RAPL1, for example, was initially reported as a gene for non-syndromic X-linked ID (34), and then subsequently was also found to harbor mutations in ASD pedigrees (9, 10). We have also identified two families in whom at least two loci may be contributing to the pathogenesis of ASD, and another seven families bearing upstream microdeletions that disrupt a complex non-coding RNA, providing possible genetic explanations for the clinical heterogeneity of these disorders. Finally, our results raise the possibility that
