In a trial of optimizing the diagnostic workflow for the introduction of WES in a diagnostic setting, we discovered another ADNP mutation in a small cohort of ID/autism patients [Helsmoortel et al., 2014a]. Targeted screening of a cohort of 148 autistic patients revealed yet another mutation. By combining the data from WES and targeted resequencing studies initiated in multiple centers, we identified a total of 10 patients with mutations in ADNP, including the cases described above [Helsmoortel et al., 2014b]. We calculated that the frequency of truncating de novo mutations in ADNP is significantly higher (p: 0.001852, odds ratio 13.24668, one-sided Fisher’s exact test) in patients compared to the ESP cohort and additional controls from the Simons Siblings. In addition to the case-control analysis, we calculated a locus specific enrichment for truncating variation using a probabilistic model as described [O’Roak et al., 2012a]. The probability of detecting eight or more de novo truncating events in ADNP within our cohort by chance was estimated to be P = 2.65e-18 (binomial test) under a de novo rate of 1.2 non-synonymous coding variants
