To characterize the spectrum of mutations in the MECP2 gene in RTT patients, we selected 46 typical RTT patients and performed mutation screening by denaturing gradient gel electrophoresis combined with direct sequencing.
Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder.
Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome.
Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been reported to cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disease.
RTT is usually associated with normal development in infancy followed by loss of acquired skills and evolution of characteristic hand wringing movements and episodes of hyperventilation.A panel of 25 female and 22 male patients with a clinical diagnosis of AS and no molecular abnormality of 15q11-13 were screened for MECP2 mutations and these were identified in four females and one male.
We show by using an inducible model of RTT that deletion of Mecp2 in adult mice recapitulates the germline knock-out phenotype, underscoring the ongoing role of MeCP2 in adult neurological function.
The novel disease alleles and benign variants of the MECP2 gene found in this study should contribute to the establishment of a reliable diagnosis of Rett syndrome.
Point mutations within the methylated DNA-binding domain of MeCP2 that cause Rett syndrome or X-linked mental retardation inhibit its interaction with ATRX in vitro and its localization in vivo without affecting methyl-CpG binding.