Identification of a de novo mutation of FOXG1gene and comprehensive analysis for molecular factors in Chinese FOXG1-related Rett syndrome

AbstractCurrently, majority of the FOXG1-related Rett syndrome have been identified in Europeans and North Americans, and relatively few Chinese cases were reported. We identified ade novononsense mutation ofFOXG1in a female child with Rett syndrome out of 73 Chinese children with neurodevelopmental disorders in our cohort. In order to have a comprehensive view of FOXG1-related disorders in China, relevant published reports were browsed and twelve cases with FOXG1 mutations or copy number variants (CNVs) involvingFOXG1gene were involved in the analysis eventually. Feeding difficulties, seizures, delayed speech, corpus callosum hypoplasia and underdevelopment of frontal and temporal lobes occurred in almost all cases. Out of the 12 cases, eight patients (66.67%) had single-nucleotide mutations (SNMs) ofFOXG1gene and four patients (33.33%) had CNVs involvingFOXG1(3 microdeletions and 1 microduplication). FOXG1 was the crucial pathological factor for FOXG1-related Rett disorder, which could be further regulated by the regulatory elements located in the intergenic region (FOXG1-PRKD1). Further analysis indicated thatPRKD1might be a contributor to the FOXG1-related Rett syndrome, which interacted with the upstream factors to regulate the expression of FOXG1, even MECP2 and CDKL5. This reanalysis might promote the existed knowledge about the molecular etiology and be helpful for diagnosis, treatment and gene therapy of FOXG1-related disorders in the future.