Non-canonical C-terminal variant of MeCP2 R344W exhibits enhanced degradation rate

Rett Syndrome (RTT) is a neurodevelopmental disorder caused by pathogenic variants in the MECP2 gene. While majority of RTT-causing are clustered methyl-CpG binding domain and NCoR/SMRT interaction domain, we report female patient with functionally uncharacterized variant C-terminal c.1030 C>T (R344W). We characterized MECP2-R344W terms protein stability, complex interaction, nuclear localization vitro. cells showed an increased degradation rate without significant change pattern, suggesting that enhanced sufficient to cause Syndrome-like phenotype. This study highlights pathogenicity Syndrome, demonstrates potential targeting stability as therapeutic approach.