Two novel mutations in the MECP2 gene in patients with Rett syndrome

Gene. 2020 Mar 30;732:144337. doi: 10.1016/j.gene.2020.144337. Epub 2020 Jan 17.


Rett syndrome (RTT) is an X-linked severe neurological disorder. Mutations in Methyl-CpG-Binding Protein2 (MECP2) gene are the main cause of RTT disease. In this study, we report the results of screening the MECP2 gene for mutations in 7 Iranian patients with RTT syndrome. MECP2 sequencing identified two novel mutations in the heterozygous state, a splice mutation, c.354G>T, p.Gly119Gly, resulting in a premature splice-donor site and a 20-bp deletion, c.1167-1186del20 (p.P390Rfs), leading to modifying the c-terminal parts of the protein and it also changes the reading frames of all coding sequence downstream of the mutation. Multiple sequence alignment showed that amino acid changes occurred in the well conserved protein regions across species. Based on the results of this study and literature reviews, about 70% of mutations are found in exon 3 and 4 of the MECP2 gene, and mutations in exon 4 are more common than other exons. Therefore, it is recommended that exon 4 to be a priority for screening the genetic analysis of RTT patients.

Keywords: DNA sequencing; MECP2 gene; Novel mutation; RTT; Rett syndrome.

MeSH terms

  • Amino Acid Sequence
  • Child
  • Exons
  • Female
  • Genotype
  • Humans
  • Iran
  • Male
  • Methyl-CpG-Binding Protein 2 / chemistry
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Mutation*
  • Phenotype
  • Rett Syndrome / genetics*
  • Sequence Homology, Amino Acid


  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2