RORa Gene Contribution to Autism; Another Epigenetic layer on Autism Complexity

Autism which occurs before age 3 is a neurogenetic disorder with a variety of impairments in social communication and speech development of children. However، recently it has been introduced as a multi-gene disorder with profound epigenetic impact on its pathology. According to the recent reports، epigenetic silencing of RORa gene (which has essential role in neural tissue development) that happen due to the methylation of its promoter region in autistic children، can explain a significant portion of the molecular pathogenesis of autism. Therefore، in current study the accuracy of this opinion was evaluated in Iranian autistic population. Methylation status of a 136 bp sequence of a CpG island in the promoter regions of RORa gene (from -64 to -200) which encompasses 13 CpG sites was examined in lymphoma cells of 30 children with autism (autistic individuals، monozygotic and dizygotic twins) and after sodium bisulfite treatment، through the Melting Curve Analysis-methylation assay (MCA-Meth) compared with normal children. Also، qRT-PCR analysis was used for evaluation of mRNA transcripts of RORa gene and confirmation of MCA-Meth analysis. In this study، no amount of methylation was found in evaluated promoter regions of healthy and unhealthy children and melting curves of all studied cases matched perfectly with unmethylated melting curves of controls. Also، qRT-PCR analysis completely confirmed the results of MCA-Meth analysis. Methylation of RORa promoter regions cannot be considered as a general epigenetic risk factor in all geographic areas and probably don’t respond any significant question about molecular pathogenesis of autism، at least in the autistic population of Iran.