Department of Neurobiology and Evelyn F. McKnight Brain Institute, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
Exp Mol Med. 2013 May 3;45(5):e21. doi: 10.1038/emm.2013.32.
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.
TCF4（转录因子 4；E2-2，ITF2）是一种转录因子，当其杂合不足时会导致 Pitt-Hopkins 综合征（PTHS），这是一种自闭症谱系障碍，与广泛的发育迟缓及严重的智力残疾有关。TCF4 基因也是精神分裂症的一个风险因素，与精神分裂症高度显著连锁，可能是通过中枢神经系统中 TCF4 基因产物的过表达。这篇综述将概述 PTHS 的临床表现，并将这些临床特征与 TCF4 的潜在分子遗传学联系起来。为了为 PTHS 中 TCF4 功能丧失提供分子生物学背景，本综述还将简要概述 TCF4 介导的细胞和神经元基因表达调控的基本生物化学。在这篇综述的最后一节中，我将讨论并推测 TCF4 转录因子在神经元功能中的可能作用，并评论了解这些作用如何为人类认知的分子神经生物学提供新的见解。
