Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by 
mutations in the MECP2 gene. Mutations have been demonstrated in more than 80% 
of females with typical features of Rett syndrome. We identified mutations in 
the MECP2 gene and documented the clinical manifestations in 65 Rett syndrome 
patients to characterize the genotype-phenotype spectrum. Bidirectional 
sequencing of the entire MECP2 coding region was performed. We diagnosed 65 
patients with MECP2 mutations. Of these, 15 mutations had been reported 
previously and 13 are novel. Two patients have multiple deletions within the 
MECP2 gene. Eight common mutations were found in 43 of 65 patients (66.15%). The 
majority of patients with identified mutations have the classic Rett phenotype, 
and several had atypical phenotypes. MECP2 analysis identified mutations in 
almost all cases of typical Rett syndrome, as well as in some with atypical 
phenotypes. Eleven (20.4%) of the 54 patients with defined mutations and in whom 
phenotypic data were obtained did not develop acquired microcephaly. Hence, 
microcephaly at birth or absence of acquired microcephaly does not obviate the 
need for MECP2 analysis. We have initiated cascade testing starting with PCR 
analysis for common mutations followed by sequencing, when necessary. Analysis 
of common mutations before sequencing the entire gene is anticipated to be the 
most efficacious strategy to identify Rett syndrome gene mutations.