MECP2 gene mutation among Iranian patients with Rett syndrome and its recurrence risk

Rett syndrome (RS) is a rare, progressive and severe neurodevelopmental disorder caused by mutations in MECP2 gene. RS usually manifest in the first couple years of life and leads to behavioral phenotypes, intellectual disabilities and brain dysfunction in females. Here, we analyzed 7 different families with at least one suspected Rett syndrome female child, diagnosed by their medical history. All of them showed a spectrum of typical phenotypes relating to Rett syndrome. We performed molecular analysis on MECP2 gene among 7 female patients. MECP2 gene amplified by polymerase chain reaction (PCR) and mutation analysis was carried out by direct sequencing. The results showed three point mutations among patients while there was not any other mutation on MECP2 among other patients. Two of them showed c.880C>T (p.R294X) mutation and the other had c.763C>T (p.R255X) mutation. Both mutations result in truncated protein and disrupt the transcription repression domain (TRD). TRD interacts with the corepressor mSin3A, which recruits histone deacetylases to form complexes for chromatin modification by MeCP2-mediated transcriptional repression. Segregation analysis showed that these mutations have occurred in the patients as de novo. This investigation revealed the importance of genetic testing for diagnosis and confirmation of the diseases that have in common phenotypes. Genetic testing could clarify and refine clinical diagnoses. Molecular analysis would help clinicians for clinical management; genotype-phenotype correlation is valuable to provide a framework for such conditions.

Keywords:

Rett syndrome , MECP2 gene , Neurodevelopmental disorder