Sensorineural Hearing Loss in Patients With the m.1555A>G Mutation in the MTRNR1 Gene

Objective: Mutations in the MTRNR1 gene of mitochondrial DNA are associated with non-syndromic hearing loss and increased susceptibility to aminoglycoside ototoxicity. The aim of our study was to determine the clinical characteristics of sensorineural hearing loss caused by the m.1555A>G mutation in MTRNR1.

Methods: An observational retrospective study of the m.1555A>G mutation was conducted in patients with suspected hereditary bilateral sensorineural hearing loss in the Department of Otolaryngology of the Marqués de Valdecilla University Hospital (Cantabria, Spain) and in 100 controls with normal hearing.

Results: The m.1555A>G mutation was found in 82 individuals from 20 different families and in none of the controls. Variable degrees of hearing loss were observed, ranging from normal hearing to profound deafness. Patients with a history of streptomycin administration exhibited significantly more pronounced hearing loss. The onset of hearing loss occurred from childhood to adulthood, with progression or stability over the years. No associated vestibular alterations or other clinical manifestations outside the ear were found. Two cochlear implant recipients showed significant improvement in speech comprehension.

Conclusions: Patients with the m.1555A>G mutation in the MTRNR1 gene often develop bilateral, symmetric sensorineural hearing loss, predominantly affecting high frequencies, worsened by streptomycin administration. This mutation does not affect the vestibular function. The variability in the severity of hearing loss, the heterogeneity of phenotypic expression, and the presence of carrier individuals with normal hearing may indicate the existence of modifying factors, both environmental and genetic. Cochlear implantees showed a good response in terms of speech intelligibility. Genetic testing for this mutation is recommended in patients with a family history of hearing loss to prevent the use of aminoglycosides if the mutation is found.

Level of evidence: 4 Laryngoscope, 2024.