Schizophrenia (SCZ) is a severe, debilitating mental illness which has a
significant genetic component. The identification of genetic factors
related to SCZ has been challenging and these factors remain largely
unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ,
we sequenced the exomes of 53 individuals with sporadic SCZ and of their
non-affected parents. We identified 49 DNVs, 18 of which were predicted
to alter gene function, including 13 damaging missense mutations, 2
conserved splice site mutations, 2 nonsense mutations, and 1 frameshift
deletion. The average number of exonic DNV per proband was 0.88, which
corresponds to an exonic point mutation rate of 1.7x10(-8) per
nucleotide per generation. The non-synonymous-to-synonymous mutation
ratio of 2.06 did not differ from neutral expectations. Overall, this
study provides a list of 18 putative candidate genes for sporadic SCZ,
and when combined with the results of similar reports, identifies a
second proband carrying a non-synonymous DNV in the RGS12 gene