Hearing Screening Combined with Target Gene Panel Testing Increased Etiological Diagnostic Yield in Deaf Children

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Congenital hearing loss (CHL) affects numerous newborns globally.
• Genetic factors are the primary cause of CHL, necessitating accurate etiological diagnosis.
• Current genetic testing strategies vary in scope and diagnostic yield.

Purpose of the Study:

• To compare the molecular epidemiology of CHL in Chinese patients using two distinct genetic testing approaches.
• To evaluate the diagnostic efficacy of a 127-gene panel versus a 159-variant test.
• To underscore the importance of comprehensive genetic analysis for CHL.

Main Methods:

• Retrospective analysis of 137 Chinese patients with CHL.
• Application of a 127-gene panel test in 63 patients.
• Application of a 159-variant test in 74 patients.
• Comparison of identified mutations and variants between the two testing methods.

Main Results:

• The 127-gene panel identified a greater number of causative genes and variants compared to the 159-variant test.
• The most frequently mutated genes identified were GJB2, SLC26A4, MYO15A, CDH23, and OTOF.
• 51 children tested with the 127-gene panel had variants not covered by the 159-variant test, indicating potential misdiagnosis with the latter.

Conclusions:

• The 127-gene panel testing demonstrates superior diagnostic yield for CHL etiology compared to the 159-variant test.
• A significant proportion of CHL cases may be misdiagnosed or undiagnosed if a limited variant test is solely relied upon.
• Broad-based genetic testing, such as the 127-gene panel, is recommended for accurate genetic diagnosis of congenital hearing loss.