Identification of Genomic Signatures in Idiopathic Mental Retardation Cases by Whole Exome Sequencing

Abstract

Intellectual disability is the most common developmental disorder characterized by a congenital limitation in intellectual functioning and adaptive behavior. Idiopathic mental retardation refers to the individuals who show no evidence of gross chromosomal defects or single-gene anomalies. Genetic factors play a major part in intellectual disability (ID), so far very few studies attempted to reveal genetic profile of the subjects, limited to few genes. The purpose of this study focused on the identification of genomic signatures in idiopathic mental retardation cases through whole exome sequencing (WES) studies. In the current study, exome sequencing of two cases revealed 29 pathogenic variations occurring in 29 genes, of which 4 variations associated with IMR were found in Case1 and 8 variations were found in Case 2. The comparison of two cases resulted in 4 common variations in both the probands. These 8 variations c.85C>T, c.185T>C, c.399C>T, c.1250A>G, c.2353C>T, c.247C>A, c.1237A>T and, c.693C>T in DPYD, HEXB, MAG, SYCE, C5/F42, PTH, CLPB and, SPATA genes respectively, were associated with intellectual disability and developmental delay. Remaining variations were associated with muscular, vision, hyperthyroidism, jaundice, etc. problems which were not shown in any of the proband of the two cases, hence suggests that probands may develop them in future. Therefore, exome sequencing could be a potential tool for unfolding causative genetic variations in non-syndromic intellectual disability.