MECP2 mutations in Danish patients with Rett syndrome: High frequency of mutations but no consistent correlations with clinical severity or with the X chromosome inactivation pattern

Rett syndrome (RTT) is a neurodevelopmental disorder, which almost exclusiv ely affects girls, who, after an initial period of apparently normal develo pment, display gradual loss of speech and purposeful hand use, gait abnorma lities and stereotypical hand movements. In the year 2000, mutations in the gene for the methyl CpG binding protein 2, MECP2, have been identified in 35-80% of the patients in three different studies. We have identified 15 di fferent MECP2 mutations in 26 of 30 Danish RTT patients. The mutations incl uded five novel mutations (one point mutation, three smaller deletions invo lving identical regions in the gene, and one duplication). In contrast to t he point mutations and the duplication, which all affect the methyl binding domain or the transcriptional repressing domain, the three overlapping del etions are clustered in the 3 ' end of the gene. We found no consistent cor relation between the type of mutation and the clinical presentation of the patient or the X-inactivation pattern in peripheral blood. Our high mutatio n detection rate, compared to two of the previous studies, underscores the importance of the inclusion criteria of the patients and supports that MECP 2 is the most important, if not the only, gene responsible for RTT.