Different Clinical Characteristics of Aminoglycoside-Induced Profound Deafness with and without the 1555 A→G Mitochondrial Mutation

The last decade has led to the identification of several mitochondrial DNA mutations associated with hearing loss. Since the only known function of the human mitochondrial chromosome is to participate in the production of chemical energy through oxidative phosphorylation, it was not unexpected that mitochondrial mutations interfering with energy production could cause systemic neuromuscular disorders, which have as one of their features hearing impairment. Surprisingly, however, inherited mitochondrial mutations also have been found to be a cause of non-syndromic hearing loss, and predispose to aminoglycoside induced hearing loss, while acquired mitochondrial mutations have been proposed as one of the causes of presbycusis. After a brief review of mitochondrial genetics, we will outline the different mitochondrial mutations associated with hearing loss, describe the audiological features, and discuss the clinical relevance of diagnosing these mutations. Clinical expression of these mitochondrial mutations is dependent on environmental exposures and nuclear-encoded modifier genes. Preventive and therapeutic strategies will depend on identification and avoidance of the environmental exposures, and the identification of the nuclear-encoded modifier genes. Experimental approaches to identify these modifier genes will be presented.

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“…This unexpected relative sparing of the vestibular system has recently been confirmed in Japanese patients (Tono et al, 2001).…”

Section: Audiological Features and Clinical Relevancementioning

confidence: 56%

Mitochondrial Deafness

Fischel‐Ghodsian

2003

Ear &Amp; Hearing

101

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“…Usually, the vestibular function is normal, which is also the case with aminoglycoside exposure. [1,3,54]. The relationship between A1555G and aminoglycoside exposure is also quite variable, and aminoglycosides seem to play a role only in approx.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature

et al. 2008

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Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial non-syndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment.

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“…Although this genetic susceptibility is present in all organs, the mitochondrial mutations target the cochlea but not the vestibular organs or the kidneys [81]. This is intriguing as this selective cochleotoxicity also occurs with preferably vestibulotoxic AGs such as streptomycin [81].…”

Section: Ototoxicity and Mechanism Of Hair Cell Damagementioning

confidence: 99%

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Huth

Ricci

Cheng

2011

International Journal of Otolaryngology

326

302

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Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.

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Different Clinical Characteristics of Aminoglycoside-Induced Profound Deafness with and without the 1555 A→G Mitochondrial Mutation

Cited by 32 publications

References 13 publications

Mitochondrial Deafness

Mitochondrial Deafness

Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

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