Array-based DNA-methylation analysis in individuals with developmental delay/intellectual disability and normal molecular karyotype

We analyzed the DNA methylation of peripheral blood samples from 81 individuals with intellectual disability (ID) and compared this methylation pattern to 19 normal controls using the HumanMethylation450 BeadChip and bisulfite pyrosequencing for validiation. We could not show a global methylation pattern that separates the patients from the normal controls. But we detected in an individual approach DNA methylation changes in the genes COLEC11, SHANK2, GLI2 and KCNQ2, known to be associated with ID, in at least one patient. DNA methylation analysis of imprinted genes revealed patients with aberrant methylation pattern at the imprinted genes PPIEL, IGF2R, MEG3 and MCTS2/HM13. Our results suggest that imprinting disorders are under-diagnosed in ID patients moreover point to DNA methylation changes as potential alternative means to deregulated genes involved in the pathogenesis of ID. Bisulfite converted DNA of peripheral blood from 82 individuals with developmental delay/intellectual disability and 19 normal controls were hybridized to the Illumina Infinium HumaneMethylation450k BeadChip.