title: 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 deletion syndrome suggests that chromosome 22q11.2 harbors the responsive genes related to the pathophysiology of schizophrenia. TheTBX1gene, which maps to the region on chromosome 22q11.2, plays a vital role in neuronal functions. Haploinsufficiency of theTBX1gene is associated with schizophrenia endophenotype. This study aimed to investigate whether theTBX1gene is associated with schizophrenia. We searched for mutations in theTBX1gene in 652 patients with schizophrenia and 567 control subjects using a re-sequencing method and conducted a reporter gene assay. We identified six SNPs and 25 rare mutations with no association with schizophrenia from Taiwan. Notably, we identified two rare schizophrenia-specific mutations (c.-123G>C and c.-11delC) located at 5' UTR of theTBX1gene. The reporter gene assay showed that c.-123C significantly decreased promoter activity, while c.-11delC increased promoter activity compared with the wild-type. Our findings suggest that theTBX1gene is unlikely a major susceptible gene for schizophrenia in an ethnic Chinese population for Taiwan, but a few rare mutations in theTBX1gene may contribute to the pathogenesis of schizophrenia in some patients.
authors.affiliation: Department of Psychiatry, Yuli Branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan. minipyng@gmail.com.
authors.forename: Lieh-Yung
authors.initials: LY
authors.lastname: Ping
authors.affiliation: Department of Psychiatry, Yuli Branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan. yc2579@gmail.com.
authors.forename: Yang-An
authors.initials: YA
authors.lastname: Chuang
authors.affiliation: Department of Psychiatry, Yuli Branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan. filvhsu@gmail.com.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: Department of Psychiatry, Yuli Branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan. ashleytsai0808@gmail.com.
authors.forename: Hsin-Yao
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Department of Psychiatry, Yuli Branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan. uncle055@yahoo.com.|Center for General Education, St. Mary's Junior College of Medicine, Nursing and Management, Yilan County 26644, Taiwan. uncle055@yahoo.com.
authors.forename: Min-Chih
authors.initials: MC
authors.lastname: Cheng
keywords: 22q11.2 deletion; TBX1; rare mutation; schizophrenia