Brain J. O’Roak, et al., Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations, doi:10.1038/nature10989
Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodeling protein network ranked significantly for autism candidate genes.
Of the severe de novo events, 28% (33 of 120) are predicted to truncate the protein.
In contrast with a recent affected and unaffected individuals; however, we do observe a trend towards increased non-synonymous rate in probands.