Screening for mutations in the TBX1 gene on chromosome 22q11.2 in Schizophrenia

Abstract

A higher-than-expected frequency of schizophrenia in patients with 22q11.2 deletionsyndrome suggests that chromosome 22q11.2 harbors the responsive genes related to thepathophysiology of schizophrenia. The TBX1 gene, which maps to the region on chromosome22q11.2, plays a vital role in neuronal functions. Haploinsufficiency of the TBX1 gene is associatedwith schizophrenia endophenotype. This study aimed to investigate whether the TBX1 gene isassociated with schizophrenia. We searched for mutations in the TBX1 gene in 652 patients withschizophrenia and 567 control subjects using a re-sequencing method and conducted a reporter geneassay. We identified six SNPs and 25 rare mutations with no association with schizophrenia fromTaiwan. Notably, we identified two rare schizophrenia-specific mutations (c.-123G>C and c.-11delC)located at 50 UTR of the TBX1 gene. The reporter gene assay showed that c.-123C significantlydecreased promoter activity, while c.-11delC increased promoter activity compared with the wild-type.Our findings suggest that the TBX1 gene is unlikely a major susceptible gene for schizophrenia inan ethnic Chinese population for Taiwan, but a few rare mutations in the TBX1 gene may contributeto the pathogenesis of schizophrenia in some patients.