title: TCF4, schizophrenia, and Pitt-Hopkins Syndrome.
abstract: Genome-wide association studies allied with the identification of rare copy number variants have provided important insights into the genetic risk factors for schizophrenia. Recently, a meta-analysis of several genome-wide association studies found, in addition to several other markers, a single nucleotide polymorphism in intron 4 of the TCF4 gene that was associated with schizophrenia. TCF4 encodes a basic helix-loop-helix transcription factor that interacts with other transcription factors to activate or repress gene expression. TCF4 mutations also cause Pitt-Hopkins Syndrome, an autosomal-dominant neurodevelopmental disorder associated with severe mental retardation. Variants in the TCF4 gene may therefore be associated with a range of neuropsychiatric phenotypes, including schizophrenia. Recessive forms of Pitt-Hopkins syndrome are caused by mutations in NRXN1 and CNTNAP2. Interestingly, NRXN1 deletions have been reported in schizophrenia, whereas CNTNAP2 variants are associated with several neuropsychiatric phenotypes. These data suggest that TCF4, NRXN1, and CNTNAP2 may participate in a biological pathway that is altered in patients with schizophrenia and other neuropsychiatric disorders.
authors.affiliation: Department of Psychological Medicine and Neurology, Medical Research Council Center for Neuropsychiatric Genetics and Genomics, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK. blakedj@cardiff.ac.uk
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Blake
authors.forename: Marc
authors.initials: M
authors.lastname: Forrest
authors.forename: Ria M
authors.initials: RM
authors.lastname: Chapman
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Tinsley
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000483:Alleles; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D001921:Brain / Q000503:physiopathology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D007805:Language Development Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D013577:Syndrome; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005819:Genetic Markers; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors