Phenotypic variability in two infants sharing the same MECP2 mutation: evidence of chromosomal rearrangements and high sister-chromatid exchange levels in Rett syndrome

Rett syndrome (RTT) whose major cause is the mutations in the X-linked MECP2 gene is a genetic disease that affects females. We screened two RTT patients using cytogenetic studies and in silico analysis as well as molecular analysis by the direct sequencing of MECP2. The cytogenetic results showed that although patient A was karyotypically normal, patient B showed chromosomal abnormalities, including chromosomal breakage in both chromosomes 2 and 5. In addition, chromosome 9 was detected on heteromorphic pattern (9ph+). A significant increase in sister-chromatid exchange (SCE) frequency was also observed in this patient. Although both patients were karyotypically different, they share the same MeCP2 mutation (p.P152R) which was predicted to be deleterious. To our knowledge, we describe the first association between MECP2 mutation, chromosomal abnormalities and high SCE frequency, which further validates the importance of the thorough chromosomal and molecular analyses that should be performed on the suspected RTT cases.