Rett syndrome is a neurodevelopmental disorder mainly caused by de novo mutations in the MECP2 (methyl-CpG-binding protein 2) gene. There is considerable variation in the severity of clinical features among Rett syndrome patients, even among patients with the same MECP2 mutation. In addition to X-chromosome inactivation pattern, the genetic background of the affected individual might also have a role in determining the severity of the disorder. We suggest that APOE is one of the genetic modulating factors. We analyzed clinical phenotypes of 46 patients with Rett syndrome, with confirmed MECP2 mutation. We discovered that among epsilon4 carriers, some clinical features were more severe, and the developmental regression occurred 4 months earlier on average than in those without the epsilon4 allele. Earlier onset of regression suggests a possible trend; however, it did not achieve distinctive statistical significance. Nevertheless, the epsilon4 allele of APOE may serve as a candidate modulation factor for the Rett syndrome phenotype.

Department of Pediatrics 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

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MECP2 mutations in Czech patients with Rett syndrome and Rett-like phenotypes: novel mutations, genotype-phenotype correlations and validation of high-resolution melting analysis for mutation scanning