Methyl-CpG-binding protein 2 (MECP2) R255X mutant pre-messenger RNA (MECP2 R255X pre-mRNA)

Methyl-CpG-binding protein 2 (MECP2) R255X mutant pre-messenger RNA is a specific transcript variant of the MECP2 gene containing a nonsense mutation (c.763C>T) that introduces a premature stop codon (p.R255X). This mutation is one of the most prevalent causes of Rett syndrome, a severe X-linked neurodevelopmental disorder that primarily affects females and is characterized by a period of normal development followed by a loss of motor and cognitive skills. The R255X mutation leads to the production of a truncated, non-functional MeCP2 protein or triggers nonsense-mediated decay, resulting in a deficiency of a protein essential for neuronal maturation and synaptic function. As a therapeutic target, this pre-mRNA is the focus of precision medicine strategies including RNA editing and nonsense suppression. RNA editing approaches, such as those developed by Vico Therapeutics, utilize antisense oligonucleotides to recruit endogenous ADAR enzymes to convert the mutant stop codon into a functional amino acid codon. Additionally, small molecule read-through agents like aminoglycosides (e.g., Gentamicin) and enhancers (e.g., CDX5-288) are being investigated for their ability to bypass the premature stop codon during translation, thereby restoring the expression of full-length, functional MeCP2 protein.

Other names

MECP2 c.763C>T pre-mRNAMECP2 p.Arg255Ter pre-mRNAMECP2 nonsense mutation pre-mRNAMECP2 R255X transcript

RNA editing (ADAR-mediated adenosine-to-inosine conversion), Nonsense suppression (translational read-through), Antisense-mediated site-blocking