Mitochondrial Hearing Loss: Genetic Variants and Clinical Progression

线粒体性听力损失:基因变异与临床进展

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Abstract

Mitochondrial diseases can affect multiple organ systems including the auditory pathway, leading to sensorineural hearing loss (SNHL). Although several mitochondrial DNA (mtDNA) mutations are linked to progressive hearing impairment, the underlying mechanisms and clinical course of mitochondrial hearing loss remain incompletely understood. In the present study, we analyzed the frequency and progression of mitochondrial mutations in 15 patients diagnosed with unexplained SNHL who underwent genetic testing at our institution. The most common mutations were m.3243A>G and m.1555A>G. Both are of particular interest due to their relatively high prevalence among mitochondrial mutations and strong clinical implications-m.3243A>G is linked to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and diabetes, while m.1555A>G is associated with aminoglycoside-induced and non-syndromic hearing loss. Hearing loss associated with m.3243A>G is generally progressive, although the rate of deterioration varies among individuals. In contrast, the m.1555A>G cases remained stable throughout the follow-up period. No significant correlation was observed between the heteroplasmy levels and hearing deterioration, although a weak negative association was observed. Despite significant hearing impairment, hearing aids are underutilized by a considerable proportion of patients. These findings provide new insights into the phenotypic variability of mitochondrial hearing loss and underscore the need for longitudinal studies to assess its natural progression and potential therapeutic interventions.

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