MECP2 Mutations Associated with Rett Syndrome - Molecular Approaches

Abstract

Rett syndrome (RTT) is defined as a monogenic, X-linked neurological disorder leading to delayed neurodevelopment in females and characterized by scoliosis, seizures, microcephaly, intellectual disability, repetitive hand movement, impaired sleep, excessive saliva, autonomic symptoms, typically little or no verbal skills. Worldwide RTT has been estimated to affect 1 in every 10-15,000 live female births in all ethnic groups [1]. Methyl-CpG binding protein 2 (MECP2) located at chromosomal position q28, containing 4 exons with five protein domains, was identified as the gene responsible for RTT in the year 1999 [2]. This gene was identified by the binding of methyl-CpG binding domain (MBD) to nucleic acid sequences that are being methylated at cytosine. Subsequently, the functional domains such as the nuclear localization signal (NLS) and transcriptional repression domain (TRD) were also identified [3]. MECP2 protein involve in various functions such as chromatin architecture, heterochromatin rearrangement, nuclear organization, regulates splicing and DNA methylation [4].