Study of MECP2 gene in Rett syndrome variants and autistic girls

Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):102-7. doi: 10.1002/ajmg.b.10070.


Mutations in MECP2 gene account for approximately 80% of cases of Rett syndrome (RTT), an X-linked severe developmental disorder affecting young girls, as well as for most cases of Preserved Speech Variant (PSV), a mild RTT variant in which autistic behavior is common. The aim of this study is to determine whether MECP2 mutations are responsible for PSV only or may cause other forms of autistic disorders. We screened for mutations by SSCP 19 girls with a clinical diagnosis of autism, two of them fulfilling the PSV criteria. A pathogenic mutation was found only in the latter two cases (R133C and R453X). A long follow-up of these two girls revealed a unique clinical course. They initially developed the first three stages of RTT, they were severely retarded and had autistic behavior. Over the years their abilities increased progressively and by early adolescence they lost autistic behavior, becoming adequately accustomed to people and reaching an IQ close to 45. These results confirm previous clinical studies suggesting that a wide spectrum of RTT exists including girls with mental abilities considerably higher than in classic RTT. We conclude that MECP2 mutations (missense or late truncating) can be found in girls with an IQ close to 45 and a clinical history of PSV of Rett syndrome. Furthermore, MECP2 mutations are not found in patients in which autism remains stable over the years.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autistic Disorder / genetics
  • Child
  • Chromosomal Proteins, Non-Histone*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Variation
  • Humans
  • Intellectual Disability
  • Methyl-CpG-Binding Protein 2
  • Mutation*
  • Repressor Proteins*
  • Rett Syndrome / genetics*
  • Speech Disorders / genetics


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins