Insights on Impact of Missense SNPs of Human USH2A associated with Usher Syndrome II

Abstract

Usher syndrome, also known as Hallgren syndrome, is an extremely rare genetic disorder caused by a mutation in any one of at least 11 genes resulting in a combination of hearing loss and visual impairment. It is a leading cause of deaf blindness and is at present incurable. Usher syndrome is classed into three subtypes according to onset and severity of symptoms. All three subtypes are caused by mutations in genes involved in the function of the inner ear and retina. Usher II are generally hard-of-hearing rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system. Usher syndrome type II occurs at least as frequently as type I, but because type II may be under diagnosed or more difficult to detect, it could be up to three times as common as type I. Usher syndrome type II may be caused by mutations in any of three different genes: USH2A, GPR98, and DFNB31. The protein encoded by the USH2A gene, usherin, is located in the supportive tissue in the inner ear and retina. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. In this study we investigate the most deleterious and disease associated SNPs in USH2A by using PolyPhen, SIFT, PANTHER, I-mutant 2.0, PhD-SNP, SNP&GO, Pmut, and Mutpred tools. The results showed mutation C759F and C536R in USH2A gene found to be most deleterious SNPs among the dataset. Our study will facilitate wet-lab researches to develop a potentdrug therapies against these USH2A mutant patients for Usher syndrome II treatment.