Influence of MECP2 Gene Mutation and X-Chromosome Inactivation on the Rett Syndrome Phenotype

Jong Hee Chae, Hee Hwang, Yong Seung Hwang, Hee Jung Cheong, Ki Joong Kim
2004 Journal of Child Neurology  
To date, approximately 200 different mutations in the MECP2 gene have been identified. We analyzed the entire coding sequence of the MECP2 gene and the X-chromosome inactivation pattern in 42 sporadic cases of Rett syndrome. Of the 42 patients, 30 had pathogenic mutations, including 14 different mutations: 9 missense mutations, 4 nonsense mutations, and 1 frameshift mutation. One was a novel mutation (S134P). There was a tendency for patients who had a nonsense mutation in the transcriptional
more » ... pression domain region to show earlier onset of regression and more severe language retardation than patients with a mutation in the methyl-CpG binding domain region. However, the parameters of clinical severity were variable among patients with the same type of mutation, depending on the pattern of X-chromosome inactivation. This study suggests that the X-chromosome inactivation pattern can modify the phenotype of Rett syndrome, which is primarily determined by the type and site of MECP2 gene mutation
doi:10.1177/08830738040190070501 pmid:15526954 fatcat:nj6qy7cx5ffmnm42sqkyvvkqaa