Abstract
Mental retardation (MR) is clinically and genetically highly heterogeneous. We have done molecular genetic testing on 85 Bulgarian MR patients who were clinically classed as fragile X syndrome (FXS) (n = 32), Rett syndrome (RTT) (n = 36) and Prader-Willi/Angelman syndromes (PWS/AS) (n = 17). We tested for the fragile X MR 1 (FMR1), methyl-CpG binding protein 2 (MECP2), cyclin dependent kinase-like 5 (CDKL5), and Aristaless X (ARX) genes, and did methylation analyses of exon 1 of the small nuclear ribonucleoprotein polypeptide N (SNRPN), and multiplex ligation-dependent probe amplification (MLPA) analyses for large deletions/duplications, and for the methylation status of FMR1 and SNRPN genes. In the FXS group we only found four mutations in the FMR1 gene (12.5%). In the RTT group we found nine mutations in the MECP2 gene (25.0%) but no CDKL5 gene mutations. In the PWS/AS group we found nine mutations in the 15q11-q13 region (53%). Thus, we clarified the molecular basis in 26.0% of the patients. The proportion of genetically proved diagnoses in our RTT patients (25.0%) is relatively high and all these cases are due to MECP2 mutations. Despite the type of mutation, all these cases are very similar from the clinical point of view and well recognized in Bulgaria.