Pitt–Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription
Open Access
- 3 May 2013
- journal article
- review article
- Published by Springer Science and Business Media LLC in Experimental & Molecular Medicine
- Vol. 45 (5), e21
- https://doi.org/10.1038/emm.2013.32
Abstract
TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt–Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system. This review will present an overview of the clinical manifestations of PTHS and relate those clinical attributes to the underlying molecular genetics of TCF4. In order to provide a molecular biological context for the loss of function of TCF4 in PTHS, the review will also present a brief overview of the basic biochemistry of TCF4-mediated regulation of cellular and neuronal gene expression. In the final section of this review, I will discuss and speculate upon possible roles for the TCF4 transcription factor in neuronal function and comment upon how understanding these roles may give new insights into the molecular neurobiology of human cognition.Keywords
This publication has 68 references indexed in Scilit:
- Genome-wide association study identifies five new schizophrenia lociNature Genetics, 2011
- A conditional knockout resource for the genome-wide study of mouse gene functionNature, 2011
- The role of the TCF4 gene in the phenotype of individuals with 18q segmental deletionsHuman Genetics, 2011
- CNTNAP2 and NRXN1 Are Mutated in Autosomal-Recessive Pitt-Hopkins-like Mental Retardation and Determine the Level of a Common Synaptic Protein in DrosophilaAmerican Journal of Human Genetics, 2009
- Experience-Dependent Epigenetic Modifications in the Central Nervous SystemBiological Psychiatry, 2009
- A Functional Genetic Link between Distinct Developmental Language DisordersThe New England Journal of Medicine, 2008
- Transcription Factor E2-2 Is an Essential and Specific Regulator of Plasmacytoid Dendritic Cell DevelopmentCell, 2008
- Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum DisordersAmerican Journal of Human Genetics, 2008
- A Common Genetic Variant in the Neurexin Superfamily Member CNTNAP2 Increases Familial Risk of AutismAmerican Journal of Human Genetics, 2008
- Linkage, Association, and Gene-Expression Analyses Identify CNTNAP2 as an Autism-Susceptibility GeneAmerican Journal of Human Genetics, 2008