Contribution of Iran in Elucidating the Genetic Causes of Autosomal Recessive Intellectual Disability

Abstract

Many genes with different inheritance modes contribute to the pathogenicity of intellectual disability (ID) making it the most known genetically heterogeneous disorder. Advanced next-generation sequencing (NGS) technologies have helped researchers identify genes underlying ID at an exponential pace. As a consanguineous country, Iran is a hotspot for discovering novel autosomal recessive intellectual disability (ARID) genes. Here, we aimed to review and compare reported ARID gene discovery both in Iran and globally, and pinpoint the research areas that need to be developed in future. We studied published articles and reviews on all known ID genes. In parallel, the gene-discovery research carried out on the Iranian population were also reviewed to determine the contribution of Iran to identifying novel ID genes. Also we tried to find supporting evidence on the causative role of novel genes identified in Iran including confirmatory functional studies and existence of more affected families. We also briefly reviewed the current therapeutic approaches under development for a subset of eligible ID cases. In total, 8% of all ID and 11.5% of all ARID genes described so far have been identified via studies on Iranian population. Functional studies have been performed on 29% of the genes identified in Iran. More than one affected family has been reported for many of these genes, supporting their causative role in ID pathogenesis. Despite the notable contribution of Iran in gene-discovery research, further functional studies on the identified genes are required.

Keywords: Autosomal recessive, Consanguineous, Intellectual disability, Iran, Next-generation sequencing