Objective: To demonstrate the efficacy and advantages of targeted exome sequencing (TES) of known deafness genes in cases with failed or misleading auditory phenotype-driven candidate gene screening.
Study design: Prospective cohort survey.
Setting: Otolaryngology department of a tertiary referral hospital.
Patients: Six hearing-impaired probands with seemingly non-syndromic features from six deaf families were enrolled in this study after failure of genetic diagnosis using auditory phenotype-driven candidate gene screening.
Intervention: TES of known deafness genes was performed in the six probands, and a final causative variant was pursued using subsequent filtering steps.
Main outcome measure: Potential causative variants determined using TES were confirmed by previously introduced filtering steps.
Results: We detected causative variants in three (50%) of six families, and these variants were in the COCH, PAX3, and GJB2 genes. Additionally, we also recapitulated the recent finding from other report arguing for the non-pathogenic potential of MYO1A variant.
Conclusions: TES of a deafness panel provides a comprehensive genetic screening tool that can be implemented without being misled by the audiogram configuration information and can complement incomplete clinical physical examinations. In addition, the secondary incidental finding obtained by TES contributes useful information regarding the deafness field.