Rett syndrome without mutations in the MECP2-Gene

Objective: In 10 to 30% of all patients with Rett Syndrome according to clinical criteria, no mutations in the MECP2-gene can be found. It was therefore speculated that there is a second gene locus for Rett Syndrome.

In this study we investigated if these girls fulfil the clinical criteria for classical Rett Syndrome. In case of classical Rett Syndrome we analysed for large deletions of the MECP2-gene and mutations in the genes encoding the histondeacetylases 1, 2 and 8.

Methods: 50 girls with suspected Rett Syndrome in whom no mutation in the MECP2-gene was detected were re-evaluated according to the diagnostic criteria for Rett Syndrome. Those grouped for classical Rett Syndrome were then further tested for large deletions by gene dosage analysis and mutations in the genes HDAC1, HDAC2 and HDAC8.

Results: 16 out of 50 fulfilled all diagnostic criteria for classical Rett Syndrome. In 5 of these 16 large deletions of the MECP2-gene were detected. So far mutations in the HDAC1, HDAC2 and HDAC8-genes were not found.

Conclusions: Most girls with suspected Rett Syndrome in whom no mutations of MECP2 were found do not fulfil the criteria for classical Rett Syndrome. In the subset of girls with classical Rett Syndrome and no mutations in the MECP2-gene frequently large deletions of the gene can be detected. Mutations of the genes encoding the histondeacetylases HDAC1, HDAC2 and HDAC8 do not seem to play a role in the pathogenesis of Rett Syndrome.

Keywords: Rett syndrome, MECP2, deletions