Sequence analysis of the entire ZIC2 protein coding regions and adjacent introns in 278 patients revealed four nonsynonymous mutations in the coding regions (Table 2). We then examined the allele frequencies of these mutations in 967 patients with schizophrenia and in 1060 control subjects (Table 2). Ins239H was the most commonly detected mutation, but its frequency (∼9%) was similar in patient and control groups. This finding is consistent with the results of previous studies724252627. The three remaining mutations, A95T, R409P, and S444R, were novel. A95T and R409P were singleton mutations not found in normal subjects. The frequency of S444R was not significantly different between the patient group (0.39%) and normal subjects (0.18%; P = 0.80 by Fisher's exact test). Patients with this mutation showed no obvious psychotic symptoms; however, we could not perform detailed physical examinations on these patients, nor examine the genotypes of their relatives because we could not obtain their consent on these issues.