Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Non-syndromic hearing loss (NSHL) presents significant genetic heterogeneity, complicating mutation identification.
• Previous studies using targeted genome enrichment (TGE) and massively parallel sequencing (MPS) primarily focused on familial hearing loss (HL) cases.
• Sporadic NSHL cases, excluding common mutations in GJB2, MT-RNR1, and SLC26A4, require effective screening methods.

Purpose of the Study:

• To assess the diagnostic utility of TGE and MPS for screening sporadic NSHL patients.
• To identify pathogenic mutations in a cohort of unrelated sporadic NSHL individuals.
• To explore the potential of genetic findings in predicting HL progression and guiding treatment.

Main Methods:

• Recruitment of 63 unrelated sporadic NSHL probands with diverse HL levels, pre-screened for common mutations.
• Application of TGE and MPS using the Human Deafness Panel oto-DA3 to analyze 131 known HL genes.
• Identification and characterization of pathogenic variants, including novel compound heterozygous mutations.

Main Results:

• Pathogenic variants were identified in 8 out of 63 patients (diagnostic rate of 12.7%).
• Identified mutations were located in genes including STRC, CATSPER2, USH2A, TRIOBP, MYO15A, GPR98, and TMPRSS3.
• Ten novel compound heterozygous mutations were discovered among the identified variants.

Conclusions:

• TGE and MPS are effective tools for diagnosing sporadic NSHL, even after excluding common mutations.
• The identification of specific pathogenic mutations can inform the prediction of hearing loss progression.
• Genetic findings offer valuable insights for the diagnosis and personalized treatment strategies in NSHL patients.