Mutation screening of the 3q29 microdeletion syndrome candidate genes DLG1 and PAK2 in schizophrenia.

Deletion of chromosome 3q29, which is associated with mental retardation and autism, was recently identified as being present in excess or occurring de novo in schizophrenia cases, being present in approximately 1/1,000 cases and 1/40,000 unscreened controls. Of the ∼20 genes in the commonly deleted region two are prominent candidates for involvement in the behavioral features of the microdeletion syndrome: DLG1 and PAK2. We report the result of mutation screening of the entire protein coding sequence of both genes in a sample of 234 unrelated cases and 272 unrelated controls from the UK. We find no evidence for any amino acid changing genetic variants in PAK2. We observe several rare and singleton non-synonymous genetic variations at DLG1, however there is no excess of these variants in cases when compared to controls. Our sample was underpowered to detect very rare or low-penetrance disease relevant alleles in the studied genes. Therefore very rare, low-to-moderate penetrance protein coding mutations or non-coding mutations at DLG1 and/or PAK2, or a nearby gene, may reproduce the behavioral characteristics of the 3q29 microdeletion.