A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients

Mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) have be en found to be a cause of Rett syndrome (RTT). In order to provide further insights into the distribution and the spectrum of mutations, we investigat ed, in addition to the whole coding sequence, a phylogenetically conserved sequence within the 3' untranslated. region (3' UTR) of the MECP2 gene for 55 sporadic RTT, including 47 typical and 8 nonclassical cases. We have dev eloped an approach based on conformation-sensitive gel electrophoresis, seq uence analysis and, for the first time, Southern blot analysis. Mutation de tection, including unreported gross DNA rearrangements, was achieved in 79% of classical RTT and 25% of nonclassical RTT patients. The high prevalence of recurrent mutations allows us to propose a molecular diagnosis strategy for RTT.