Genetic background in late-onset sensorineural hearing loss patients

Area of Science:

• Genetics
• Otolaryngology
• Medical Diagnostics

Background:

• Genetic testing is common for early-onset hearing loss, but less so for late-onset forms due to perceived complexity and lower diagnostic rates.
• The exact causes of late-onset hearing loss remain largely unknown.
• Late-onset hearing loss is often considered complex, with limited understanding of its genetic underpinnings.

Purpose of the Study:

• To investigate the genetic etiology of late-onset bilateral sensorineural hearing loss in Japanese patients.
• To determine the diagnostic yield of genetic testing in a cohort of late-onset hearing loss cases.
• To identify specific genes and variants associated with late-onset hearing loss and expand phenotypic descriptions.

Main Methods:

• Recruited 48 unrelated Japanese patients diagnosed with late-onset bilateral sensorineural hearing loss.
• Conducted genetic analysis using massively parallel DNA sequencing.
• Examined 63 known deafness genes for causative variants.

Main Results:

• Identified 25 possibly causative variants in 29 patients, achieving a diagnostic rate of 60.4%.
• Confirmed that diverse genes contribute to late-onset hearing loss, with a significant genetic component.
• Described two unique cases: one with a novel MYO7A variant showing progressive hearing loss and retinitis pigmentosa, and another with Stickler syndrome due to a COL9A3 variant.

Conclusions:

• A significant proportion of late-onset hearing loss cases are genetically determined.
• Comprehensive genetic testing is essential for accurate diagnosis and personalized treatment of late-onset hearing loss.
• Genetic analysis can uncover novel variants and expand the understanding of hearing loss phenotypes.