# Comprehensive Genetic Evaluation in Patients with Special Reference to Late-Onset Sensorineural Hearing Loss

## TL;DR

This study shows that genetic factors contribute to late-onset hearing loss, suggesting genetic testing is valuable even for older patients.

## Contribution

The study provides a comprehensive genetic evaluation of late-onset hearing loss, revealing a significant diagnostic yield.

## Key findings

- A diagnostic rate of 31.9% was achieved using next-generation sequencing in 91 hearing loss patients.
- Genetic causes were identified in 55.9% of patients with familial history and progressive hearing loss.
- The diagnostic rate decreased with age, but genetic factors remained relevant even in late-onset cases.

## Abstract

Hearing loss (HL) is a common and multi-complex etiological deficit that can occur at any age and can be caused by genetic variants, aging, toxic drugs, noise, injury, viral infection, and other factors. Recently, a high incidence of genetic etiologies in congenital HL has been reported, and the usefulness of genetic testing has been widely accepted in congenital-onset or early-onset HL. In contrast, there have been few comprehensive reports on the relationship between late-onset HL and genetic causes. In this study, we performed next-generation sequencing analysis for 91 HL patients mainly consisting of late-onset HL patients. As a result, we identified 23 possibly disease-causing variants from 29 probands, affording a diagnostic rate for this study of 31.9%. The highest diagnostic rate was observed in the congenital/early-onset group (42.9%), followed by the juvenile/young adult-onset group (31.7%), and the middle-aged/aged-onset group (21.4%). The diagnostic ratio decreased with age; however, genetic etiologies were involved to a considerable degree even in late-onset HL. In particular, the responsible gene variants were found in 19 (55.9%) of 34 patients with a familial history and progressive HL. Therefore, this phenotype is considered to be a good candidate for genetic evaluation based on this diagnostic panel.