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.
CONCLUSION: 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.