title: Molecular characteristics of Chinese patients with Rett syndrome.
abstract: OBJECTIVE
  Rett syndrome (RTT) is a neurodevelopmental disorder which affects 1/10,000 girls. The aim of this study is to delineate the molecular characteristics of Rett syndrome in China based on the largest group of Chinese patients ever studied.
  
  
  METHODS
  In all, 365 Chinese patients with Rett syndrome were recruited. Clinical information including the family reproductive history was collected through interviewing patients and their parents as well as questionnaires. MECP2, CDKL5, FOXG1 mutational analysis was performed using polymerase chain reaction (PCR), direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The parental origin of mutated MECP2 gene, the MECP2 gene mutation rate in the patients' mothers, and the X-chromosome inactivation pattern of the mothers who carry the mutation were also analyzed.
  
  
  RESULTS
  Almost all of the patients were sporadic cases except one pair of twins. The pregnancy loss in probands' mothers and sex ratio of offspring in probands(') generation were available in 352 families and were comparable to the general population. Out of the 365 cases, 315 had MECP2 gene mutations and 3 had de novo CDKL5 gene mutations. No patients had FOXG1 mutation. Among the 315 cases with MECP2 mutations, 274 were typical cases and 41 were atypical cases. All the 3 cases with CDKL5 gene mutations were atypical RTT with early-onset seizures. The analysis of parental origin of mutated MECP2 gene were performed on 139 cases, 90 (64.7%) cases were informative for the study. The result showed 94.4% cases with mutations from paternal origin and 5.6% from maternal origin. Among the cases with paternal mutation, 90.6% had point mutations. C > T was the most common one, accounting for 85.7% of the point mutations. Only one normal phenotype mother (0.41%) carried the same p.R133C mutation of MECP2 gene as her daughter with mild phenotype. The different patterns of X-chromosome inactivation in the mother and the daughter may explain their different phenotypes.
  
  
  CONCLUSIONS
  The high rate of paternal origin of the mutated MECP2 gene may explain the high occurrence of RTT in female gender. The family cases of RTT are rare and the recurrence risk of RTT is very low in China. Only 0.41% (1/244) mothers carry the pathogenic gene. FOXG1 mutations were not found in this group of Chinese patients.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Bao
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Guangna
authors.initials: G
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Wei
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D050172:Genes, X-Linked; D006801:Humans; D007223:Infant; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human