Mutation spectrum in the gene encoding methyl-CpG-binding protein 2 in Egyptian patients with Rett syndrome

Abstract Rett syndrome (RTT) is a monogenic neurodevelopmental disorder caused primarily by mutations in the MECP2 gene. This study presents the spectrum of MECP2 mutations in 50 Egyptian RTT females with identified gene mutation. Molecular analysis was carried out by direct sequencing of the gene coding region, followed by multiplex ligation-dependent probe amplification (MLPA) for patients without detected pathogenic variation. In total, 23 different disease-causing mutations, including 5 novel frameshift mutations, have been reported. In the study cohort, T158 M is the most common mutation (18%), followed by R270X (14%). Large rearrangements account for 10% of cases intensifying the emergency of gene quantitative analysis. This study provides an effective and simple instrument for molecular analysis of MECP2 gene and genetic counseling of RTT cases.