Mutation analysis of the MECP2 gene in Romanian females with Rett syndrome

The discovery of the methyl-CpG binding protein 2 (MECP2) gene located on Xq28 as being involved in Rett syndrome (RTT) has been followed by a broad spectrum of phenotypes being associated with mutations in MECP2. The distribution of MECP2 mutations has been studied in many populations, but only recently in Romania. We started the first local study searching for MECP2 mutations using PCR (polymerase chain reaction) - based methods and Sanger sequencing. We have investigated 9 patients, all girls, 7 with classical RTT and 2 with atypical RTT from the Western part of Romania. Mutation screening revealed 3 different mutations present in 4 patients and 5 nonpathogenic genetic variations. One of the frameshift mutations has not been previously described: c.225delG (p.P75fs). The detection rate for missense and frameshift mutations was 44 %. In this study we focused on a practical approach necessary for the molecular geneticist in the process of screening RTT patients for MECP2 mutations. The aim is to extend this protocol for screening MECP2 mutations in all cases of MECP2-related Disorders, to offer prenatal diagnosis, and subsequently complete it with techniques which can detect large rearrangements of this gene.