PMC:4067558 / 31389-33108 JSONTXT

{"project":"2_test","denotations":[{"id":"24768552-22495311-2047140","span":{"begin":1244,"end":1246},"obj":"22495311"},{"id":"24768552-23708187-2047140","span":{"begin":1244,"end":1246},"obj":"23708187"},{"id":"24768552-23020937-2047140","span":{"begin":1244,"end":1246},"obj":"23020937"}],"text":"We further characterized the biological processes related to the NETBAG cluster (Tables S14B–S14E; Figures 4B and S3) and found a significant enrichment (false-discovery rate [FDR] \u003c 10%) of genes involved in chromatin and transcription regulation, MAPK signaling, and synaptic signaling and components (Figure 4B). We recapitulated many of the results of our gene-set analysis (Figure 4A), notably for synapse functions and processes, and also identified genes involved in chromatin and transcription regulation. The latter category included a high-risk gene associated with ASD, the chromatin gene CHD2 (MIM 602119), which is affected by a de novo 83 kb deletion in a male with ASD, mild ID, and dysmorphic features including micrognathia and protruding ears. His ASD-affected brother has mild ID, similar dysmorphic features, and epilepsy with onset at age 9 years and carries the same deletion, which removes the first six exons of CHD2. Neither parent carries the deletion, suggesting germline mosaicism (the deletion arose on the paternal chromosome). De novo SNVs in CHD2 have been reported in an ASD subject and in several individuals with a broad spectrum of neurodevelopmental disorders, including ID and epileptic encephalopathy8,49,50 (Figure S6). Two other genes in the chromodomain family have been linked to neurodevelopmental disorders: CHD7 (MIM 608892) in CHARGE syndrome (MIM 214800) and CHD8 (MIM 610528) in ASD. Another example is TRIP12 (MIM 604506), encoding an E3 ubiquitin ligase that can regulate chromatin function to maintain genome integrity (Figure S12). The chromatin and transcription module showed a predominance of genes with a prenatally biased expression profile (Figures 4B and S4)."}