Author/Authors :
SALEHI، MANSOOR نويسنده , , Kamali، Elahe نويسنده Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran , , KARAHMADI، MOJGAN نويسنده , , Mousavi، Seyyed Mohammad نويسنده Behavioral and Neurosciences Research Center ,
Abstract :
Objective: Autism is a neurodevelopmental disorder characterized by difficulty in verbal
and non-verbal communication, impaired social interaction, and restricted and repetitive
behavior. It has been recently introduced as a multigenic disorder with significant epigenetic
effects on its pathology. Recently, epigenetic silencing of retinoic acid receptorrelated
orphan receptor alpha (ROR?) gene (which has an essential role in neural tissue
development) was shown to have occurred in autistic children due to methylation of its
promoter region. This may thus explain a significant part of the molecular pathogenesis
of autism. Therefore, we aimed to confirm this finding by implementing a case-control
(experimental) study in the population of Isfahan.
Materials and Methods: The methylation status of a 136 bp sequence of a GpG island
(encompassing 13 CpG sites) in the RORA promoter region (positions -200 to -64) as an
experimental study was examined in the lymphocyte cells of 30 autistic children after sodium
bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay
compared with normal children. Also, quantitative reverse transcriptase-polymerase chain
reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to
evaluate MCA-Meth analysis results.
Results: This study revealed no methylation in the examined promoter regions in both
autistic and normal children, with the melting curve of all studied samples being comparable
to that of the non-methylated control. The results of MCA-Meth analysis were also
consistent with qRT-PCR results. We therefore observed no significant difference in the
levels of ROR? transcripts in the blood lymphocytes between autistic and healthy children.
Conclusion: The methylation of the RORA promoter region may not be considered as a
common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis
of autism remains unclear in the population investigated.
