Mostafa Saghi - Genetic Research Center, University of social welfare and Rehabilitation Sciences, Tehran, Iran
Kolsoum InanlooRahatloo - School of Biology, College of Science, University of Tehran, Iran
Afagh Alavi - Genetic Research Center, University of social welfare and Rehabilitation Sciences, Tehran, Iran
Kimia Kahrizi - Genetic Research Center, University of social welfare and Rehabilitation Sciences, Tehran, Iran

Introduction: Intellectual disability (ID) is a clinically important disease and a most prevalent neurodevelopmental disorder. The etiology and pathogenesis of ID are poorly recognized. Polr3b gene encoding the second largest subunit of RNA polymerase III and diseases associated with mutation in this gene are Hypomyelinating leukodystrophy-8 With or Without Oligodontia And/Or Hypogonadotropic Hypogonadism and Pol III-Related Leukodystrophies. Method: To explore how genetic variants alter cell expression in ID patients, RNA sequencing on blood samples was performed. Exome sequencing revealed a homozygous missense mutation in the Polr3b gene in one ID family and to obtain insights into the biological pathways influenced by Polr3b mutation, we applied our RNA-Seq data to several gene ontology programs such as BioCarta, WikiPathways, KEGG, NCI-Nature and panther Result: Overall, 509 differentially expressed genes (p-value <0.05 and fold change> 1.5) were identified between POLR3B mutant patients and controls, of these 509 genes, 225 genes downregulated and 284 genes upregulated in ID patients. in addition to involving immune and translation systems, the most significantly dysregulated pathways were " Nonsense Mediated Decay", " Cell adhesion molecules (CAMs) ", "NOD-like receptor signaling pathway" and some metabolism pathways such as "Selenocysteine synthesis", "Arylamine" and "Sulfur".Conclusion: The current study highlights the importance of NMD and CAM molecular pathways in intellectual disability and highlights the importance of POLR3B in neuronal functions.

Intellectual Disability, POLR3B, RNA-Seq