Mutation in (GJB3 and GJB4) Genes involved in Deafness in two Sudanese Families Using Next Generation Sequencing

generation sequencing (NGS) technology becomes the premier tool in genetic and genomic analysis by offering high-throughput sequencing.The identification of causer variant of genetic disease became a great challenge. Various in silico bioinformatics tools have been used to predict deleterious effect of mutation associated with hearing impairment among Sudanese patients. Our aim was to explore whether other genes, than those reported single nucleotide polymorphisms (SNPs), associated with deafness are found among Sudanese patients using multiple algorithms tools. NGS data of two Sudanese families were analyzed in silico. The potentially functional nonsynonymous single nucleotide polymorphisms (nsSNPs) and their effect on protein was predicted by Polymorphism Phenotype (PolyPhen) and Sort Intolerant from Tolerant (SIFT) softwares, respectively. Protein stability change was calculated using I-Mutant 2.0. University of California, San Francisco (UCSF) chimera software was used to compare between the 3D structure of wild and mutant type of proteins. Our analysis showed deleterious nsSNP's in GJB3 and GJB4 genes ranging from 0.00-0.05 (SIFT), >1.50 (Polyphen) and decrease protein activity (I-mutant), and accordingly the candidate genes were selected as a causative variant of hearing impairment in two Sudanese families. In conclusion, NGS provides data to facilitate the discovery of variants associated with hearing impairment. The accuracy of deleterious nsSNPs predicted can be increased by combining different computational methods as SIFT, Polyphen2 and I-Mutant 2.0.