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

ABSTRACT: 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) and TMPRSS3 (c.941?T?>?C). The remaining 2 pedigrees each contained two candidate variants: TECTA (c.4045G?>?A) and MYO15A (c.3310G?>?T and c.9913G?>?C) for one pedigree and DFNB59 (c.494G?>?A) and TRIOBP (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.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC7368710 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature