Epigenetic approach of Prader-Willi syndrome diagnosis in Romanian population

This work aimed to compare the clinical validity of a newly developed assay for Prader-Willi syndrome diagnosis in Romanian population, as compared to an existing assay. This syndrome is a complex multisystem, genetic and epigenetic disorder, which arises from a defect in imprinted genes regulation and contribution. So far, a molecular cytogenetic method (fluorescence in situ hybridization) has been the most frequently used assay in primary diagnosis, but because it is targeted towards genetic factors it only covers deletional cases in this pathology. However, gene expression control is realized both through physical presence of the corresponding DNA sequence and through specific methylation patterns on parental alleles of the given gene: normal healthy state is defined by unmethylated (expressed) paternal allele, in the presence of methylated (repressed) maternal allele; by contrast, the pathological condition is defined by the presence of only methylated (repressed) maternal allele, thus the lack of unmethylated (contributing) paternal allele. This is the first report presenting a methylation mapping assay, based on methylation specific amplification, for Prader-Willi syndrome in Romanian population, suggesting it might be used as primary diagnosis tool based on its cost-efficiency and covering ability of almost entire Prader-Willi syndrome etiology (deletions, unimaternal disomy, imprinting defect).