Whole exome sequencing revealed novel variants in consanguineous Pakistani families with intellectual disability

Background Intellectual disability (ID) is a heterogeneous disorder affecting 1–3% of the population. Elucidation of monogenic variants for ID is a current challenge. These variants can be better demonstrated in consanguineous affected families. Objective The study was designed to find the genetic variants of ID in consanguineous families. Methods We analyzed five unrelated consanguineous Pakistani families affected with ID using whole exome sequencing (WES). Data was analyzed using different bioinformatics tools and software. Results We mapped four variants including three novels in four different ID known genes. Each variant is found in a different family, co-segregating with a recessive pattern of inheritance. The novel variants found are; c. 2_4del (p.?) mapped in ROS1 and c. 718G>A (p.Gly240Arg) in GRM1. Another novel causative variant, c.2673del (p.Gly892Aspfs*17) identified in COL18A1 in a recessive form, a gene reported for Knobloch syndrome that manifests ID along with typical retinal abnormalities, and this phenotype was confirmed on reverse phenotyping. A mutation c.2134C>T (p.Arg712*) in TRAPPC9 has been found first time in the homozygous recessive form in our enrolled three affected siblings while it was previously reported in compound heterozygous form in a Caucasian descent. While fifth family remained unsolved. Conclusion These mutations in four different genes with a recessive inheritance would be a contribution to the disease variant database of this devastating disorder.