Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistani families

Background Hearing loss is the most common sensory defect, and it affects over 6% of the population worldwide. Approximately 50-60% of hearing loss patients are attributed to genetic causes. Currently, more than 100 genes have been reported to cause non-syndromic hearing loss. It is possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES). Methods We collected 5 consanguineous pedigrees from Pakistan with hearing loss and applied WES in selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causal genes. Results Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate variant for 3 pedigrees:GIPC3(c.937 T > C),LOXHD1(c.6136G > A) andTMPRSS3(c.941 T > C). The remaining 2 pedigrees each contained two candidate variants:TECTA(c.4045G > A) andMYO15A(c.3310G > T and c.9913G > C) for one pedigree andDFNB59(c.494G > A) andTRIOBP(c.1952C > T) for the other pedigree. The candidate variants were validated in all available samples by Sanger sequencing. Conclusion The candidate variants in hearing-loss genes were validated to be co-segregated in the pedigrees, and they may indicate the aetiologies of hearing loss in such patients. We also suggest that WES may be a suitable strategy for hearing-loss gene screening in clinical detection.