Inherited susceptibility to aminoglycoside ototoxicity: Genetic heterogeneity and clinical implications

Casano, Rosaria A.M.S.; Johnson, David; Bykhovskaya, Yelena; Torricelli, Francesca; Bigozzi, Minna; Fischel‐Ghodsian, Nathan

doi:10.1016/s0196-0709(99)90062-5

Cited by 133 publications

(88 citation statements)

References 12 publications

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“…Three additional observations support the concept that mitochondria play a key role in mediating aminoglycoside ototoxicity. First, patients with mutations of the mitochondrial ribosomal RNA are predisposed to aminoglycoside-induced hearing loss (Prezant et al 1993;Estivill et al 1997;Casano et al 1999). Second, concurrent addition of chloramphenicol, a specific mitochondrial poison, has been shown to increase the extent of gentamicin-induced FIG.…”

Section: Discussionmentioning

confidence: 99%

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cheng

Cunningham

Rubel

2003

JARO - Journal of the Association for Research in Otolaryngolog

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Caspases are a family of proteases that have been implicated as key mediators of cell death. Although nonspecific inhibition of caspase activation has been reported to prevent mammalian sensory hair cell death, the exact roles of individual caspases during hair cell death are unclear. In other systems, the activation of initiator caspases, such as caspase-8 and caspase-9, can lead to the activation of the effector caspase-3. We have begun to systematically characterize hair cell death in an in vitro system by examining the activation of these specific caspases in degenerating hair cells after acutely damaging the whole avian basilar papilla with gentamicin. Basilar papillae (BP) displayed a dose-dependent hair cell loss after a 24-h treatment with gentamicin at concentrations of 0.1, 0.5, and 2.0 mM. When treated with 0.5 mM gentamicin for 6, 12, or 24 h, hair cells first began to degenerate in the basal third of the BP and damage progressed apically. Supplementation of z-VAD-fmk, a general caspase inhibitor, provided short-term protection against gentamicin-induced hair cell death. Treatment with gentamicin for 6 or 12 h promoted the expression of active caspase-3 and active caspase-9 in many hair cells along the BP as shown by immunohistochemistry. At these timepoints, specific fluorescent-labeled peptide substrates detected more active caspase-3, caspase-8, and caspase-9 in gentamicin-treated hair cells relative to controls. Our data indicate that auditory hair cells degenerate as a result of gentamicin exposure in a caspase-dependent manner. Specifically, the upstream caspases, caspase-8 and caspase-9, and the downstream caspase-3 are activated in aminoglycoside-damaged hair cells.

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Section: Discussionmentioning

confidence: 99%

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cheng

Cunningham

Rubel

2003

JARO - Journal of the Association for Research in Otolaryngolog

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“…The C1494T mutation in the highly conserved decoding site of the 12S rRNA has been associated with both aminoglycoside-induced and nonsyndromic hearing loss in a large Chinese family [Zhao et al, 2004a;Zhao et al, 2005]. Mutations at position 961 of the 12S rRNA have been implicated to be associated with both aminoglycoside-induced and nonsyndromic hearing loss [Casano et al, 1999;Li et al, 2004a]. Furthermore, the T1095C mutation in the same rRNA has also been shown to be associated with hearing impairment in several genetically unrelated families [Thyagarajan et al, 2002;Zhao et al, 2004b;Li et al, 2005c].…”

Section: Introductionmentioning

confidence: 99%

Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA^Ser(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside‐induced and nonsyndromic hearing loss

Yuan

Qian

Yang

et al. 2005

American J of Med Genetics Pt A

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We report here on the characterization of a three-generation Chinese family with aminoglycosideinduced and nonsyndromic hearing impairment. Ten of 17 matrilineal relatives exhibited bilateral and sensorineural hearing impairment. Of these, nine matrilineal relatives, who had a history of exposure to aminoglycosides, exhibited variable severity and audiometric configuration of hearing loss. The dose and age at the time of drug administration seemed to be correlated with the severity of the hearing loss experienced by affected individuals. Sequence analysis of the complete mitochondrial genome in the pedigree showed the presence of homoplasmic A1555G mutation and 37 variants belonging to haplogroup D4a. Of those variants, the G7444A mutation is of special interest as the mutation at this position results in a read-through of the stop condon AGA of the COI message, thereby adding three amino acids (Lys-Gln-Lys) to the C-terminal of the polypeptide. Alternatively, the G7444A mutation is adjacent to the site of 3' end endonucleolytic processing of L-strand RNA precursor, spanning tRNA Ser(UCN) and ND6 mRNA. Thus, the G7444A mutation, similar to the deafness-associated A7445G mutation, may lead to a defect in the processing of the L-strand RNA precursor, thus influencing the phenotypic expression of the A1555G mutation. These data also imply that nuclear background plays a role in the aminoglycoside ototoxicity associated with the A1555G mutation in this Chinese pedigree.

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“…Recently, the C1494T mutation in the same gene has been associated with both aminoglycoside induced and nonsyndromic hearing loss in a large Chinese family [Zhao et al, 2004]. In addition, a C-insertion or deletion at position 961 of the 12S rRNA gene has been shown to be associated only with aminoglycoside-induced deafness [Bacino et al, 1995;Casano et al, 1999], while the novel T961G mutation has been implicated to be responsible for the nonsyndromic hearing loss in five Caucasian pediatric subjects [Li et al, 2004a]. Furthermore, the T1095C mutation has also been shown to be associated with hearing impairment [Thyagarajan et al, 2000;Tessa et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular characterization of a Chinese patient with auditory neuropathy associated with mitochondrial 12S rRNA T1095C mutation

Wang

Zhao

et al. 2005

Am. J. Med. Genet.

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Mutations in mitochondrial DNA (mtDNA), particularly those in the 12S rRNA gene, have been shown to be associated with sensorineural hearing loss. Recently, a systematic and extended mutation screening of the mitochondrial 12S rRNA gene has been initiated in the large clinical population of the Otology Clinic at the Chinese PLA General Hospital with the aim of identifying mtDNA mutations associated with hearing loss. Here we report the clinical and molecular characterization of a Chinese patient with auditory neuropathy. Sequence analysis of mtDNA in this patient identified a T-to-C transition at position 1095 (T1095C) in the 12S rRNA gene and other nucleotide changes. The T1095C mutation is expected to disrupt an evolutionarily conserved A-to-U base-pair, which is at the highly conserved P-site of 12SrRNA. TheT1095C mutation has also been found to be associated with hearing loss in several unrelated families. Among other nucleotide changes, two novel variants: the I175V mutation in the CO2 and the V112M mutation in the ND6 localize at highly evolutionarily conserved residues from different organisms. Furthermore, the absence of mutation in the otoferlin related to auditory neuropathy showed that otoferlin may not be involved in the phenotypic expression of T1095C mutation in this subject. These data suggest that the T1095C mutation may be associated with auditory neuropathy in this subject, and two novel variants I175V and V112M may play a role in the phenotypic expression of the T1095C mutation.

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Inherited susceptibility to aminoglycoside ototoxicity: Genetic heterogeneity and clinical implications

Cited by 133 publications

References 12 publications

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA^Ser(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside‐induced and nonsyndromic hearing loss

Clinical and molecular characterization of a Chinese patient with auditory neuropathy associated with mitochondrial 12S rRNA T1095C mutation

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Inherited susceptibility to aminoglycoside ototoxicity: Genetic heterogeneity and clinical implications

Cited by 133 publications

References 12 publications

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cosegregation of the G7444A mutation in the mitochondrial COI/tRNASer(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside‐induced and nonsyndromic hearing loss

Clinical and molecular characterization of a Chinese patient with auditory neuropathy associated with mitochondrial 12S rRNA T1095C mutation

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Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA^Ser(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside‐induced and nonsyndromic hearing loss