Whole-Transcriptome Analysis Reveals Dysregulation of Actin-Cytoskeleton Pathway in Intellectual Disability Patients

Abstract A significant level of genetic heterogeneity has been demonstrated in intellectual disability (ID). More than 700 genes have been identified in ID patients. To identify molecular pathwaysunderlying this heterogeneity, we applied whole-transcriptome analysis using RNA-Seqin consanguineousfamilies with ID. Significant changes in expression of genes related to neuronal and actin cytoskeletal functions were observed in all the ID families. Remarkably, we found a significant down-regulation of SHTN1 gene and up-regulation of FGFR2 gene in all ID patients. FGFR2, but not SHTN1, was previously reported as an ID causing gene. Detailed gene ontology analyses identified pathways linked to tyrosine protein kinase, actin cytoskeleton, and axonogenesisto be affected in ID patients. The findings reported here provide new insights into the candidate genes and molecular pathwaysunderling ID and highlight the key role of actin cytoskeletonin etiology of ID.