AbstractA modified method of differential display was employed to identify a novel gene (namedPSZA11q14), the expression of which was reduced in brains from patients with schizophrenia. Decreased expression ofPSZA11q14was identified initially in Brodmann's area (BA) 21 from a small group of patients with schizophrenia (n= 4) and normal controls (n= 6) and was confirmed subsequently using independent RT‐PCR assay in BA 21, 22, and 9, and in hippocampus from a larger group of patients with schizophrenia (n= 36) and controls (n= 35).PSZA11q14is located on chromosome 11q14, an area shown previously to co‐segregate with schizophrenia and related disorders in several families. Decreased expression ofPSZA11q14in patients with schizophrenia and its location on 11q14 provide converging lines of evidence indicating thatPSZA11q14may be involved in at least some cases of schizophrenia.PSZA11q14shows no significant homology with any known gene. It has no introns and produces two RNA transcripts of ∼4.5 and ∼7.0 kb. The largest open reading frame (ORF) in thePSZA11q14transcripts may potentially encode for a short polypeptide of 71 amino acids. High frequency of rare codons, the short size of this ORF, and low homology with mouse sequences, however, indicate thatPSZA11q14may instead represent a novel member of a family of nonprotein‐coding RNA genes that are not translated and that function at the RNA level.PSZA11q14is located within the first intron of theDLG‐2gene and transcribed in the opposite direction toDLG‐2. These results suggest thatPSZA11q14may be considered a candidate gene for schizophrenia acting as an antisense regulator ofDLG‐2, which controls assembling functionalN‐methyl‐D‐aspartate (NMDA) receptors. © 2003 Wiley‐Liss, Inc.