FOXG1-Related Disorders: From Clinical Description to Molecular Genetics

Molecular Syndromology

C. Florian¹  T. Bienvenu¹  N. Bahi-Buisson¹ 

[1] aInserm, U1016, Université Paris Descartes, CNRS (UMR 8104), Paris, France

关键词: Chromosome 14;    Clinical features;    Congenital variant;    Encephalopathy;    FOXG1;    Human;    Microcephaly;    Molecular basis of disease;    Mouse;    Rett syndrome;   

DOI  :  10.1159/000327329

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

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 Rett-like 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.

【 授权许可】

Unknown