FOXG1-Related Disorders: From Clinical Description to Molecular Genetics
FOXG1-Related Disorders: From Clinical Description to Molecular Genetics
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DOI：
10.1159/000327329
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发表时间：
2011-01-01
影响因子：
1.1
通讯作者：
Bienvenu, T.
中科院分区：
文献类型：
--
作者：
Florian, C.;Bahi-Buisson, N.;Bienvenu, T.
Rett综合征（RTT）是一种严重的神经发育疾病，大约每10,000名活产女性中就有1人患病，通常由编码甲基cpg结合蛋白2 （MECP2）的x连锁基因突变引起。在标记为非典型RTT的个体中也发现了MECP2以外的位点突变。其中叉头盒G1 （FOXG1）基因突变参与了RTT先天性变异的分子病因学。FOXG1基因编码对胚胎前脑腹侧端脑发育至关重要的翼螺旋转录抑制因子。随后，FOXG1继续在出生后大脑的神经遗传区表达。尽管RTT几乎只影响女孩，但在男性患者中也发现了FOXG1突变。据我们所知，文献中描述了大约12例点突变和13例FOXG1分子异常（包括14q12染色体易位、重复和大缺失）。FOXG1突变的受影响个体表现出畸形特征和rett样临床病程，包括围产期正常、产后小头畸形、癫痫发作和严重智力低下。有趣的是，现有的FOXG1缺乏症动物模型显示出类似的表型，这表明动物模型可能是了解这种人类疾病的一个有趣的模型。在这里，我们描述了人类和小鼠模型中FOXG1突变及其相关表型的影响。巴塞尔S. Karger股份有限公司版权所有
Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Mutations in loci other than MECP2 have also been found in individuals that have been labeled as atypical RTT. Among them, a mutation in the gene forkhead box G1 (FOXG1) has been involved in the molecular aetiology of the congenital variant of RTT. The FOXG1 gene encodes a winged-helix transcriptional repressor essential for the development of the ventral telencephalon in embryonic forebrain. Later, FOXG1 continues to be expressed in neurogenetic zones of the postnatal brain. Although RTT affects quasi-exclusively girls, FOXG1 mutations have also been identified in male patients. As far as we know, about 12 point mutations and 13 cases with FOXG1 molecular abnormalities (including translocation, duplication and large deletion on the chromosome 14q12) have been described in the literature. Affected individuals with FOXG1 mutations have shown dysmorphic features and Rettlike clinical course, including normal perinatal period, postnatal microcephaly, seizures and severe mental retardation. Interestingly, the existing animal models of FOXG1 deficiency showed similar phenotype, suggesting that animal models may be a fascinating model to understand this human disease. Here, we describe the impacts of FOXG1 mutations and their associated phenotypes in human and mouse models. Copyright (C) 2011 S. Karger AG, Basel