The FOXG1-related syndrome with two novel mutations in the FOXG1 gene

Rett syndrome (RTT) is a rare neurological disorder with a range of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2) gene are found in >95% of typical form and 50–70% of atypical form of Rett syndrome. Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) genes are associated with specific RTT variants. This study was carried out to identify the gene mutations in patients with symptoms related to congenital Rett syndrome. Possible causative variations were identified using whole exome sequencing (WES) in two patients. Two novel pathogenic variants (c.563C > A, p.Ala188Glu and c.653A > G, p.Tyr218Cys) were detected in the FOXG1 gene, associated with congenital Rett syndrome. Moreover, other reported variants were also found in the KIF5A and KMT2D genes. In-silico analysis of FOXG1 variants showed that amino acid changes occurred in the conserved domain among different species that altered the conformation of FoxG1 protein; thereby, disrupting the protein function. Our findings extend the variety of mutations in the FOXG1 gene, which cause FOXG1-related syndrome.