Influence of MECP2 gene mutation and X-chromosome inactivation on the Rett syndrome phenotype.
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 repression 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.
Chae
Jong Hee
JH
Department of Pediatrics, Seoul National University College of Medicine, 28 Yongon-dong, Jongnogu, Seoul 110-744, Korea.
Hwang
Hee
H
Hwang
Yong Seung
YS
Cheong
Hee Jung
HJ
Kim
Ki Joong
KJ
D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D018899:CpG Islands; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*; D012720:Severity of Illness Index
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins