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ERIC Number: EJ846280
Record Type: Journal
Publication Date: 2005
Pages: 17
Abstractor: As Provided
Reference Count: 0
ISBN: N/A
ISSN: ISSN-0042-8639
Prevalence of Mitochondrial 12S rRNA Mutations Associated with Aminoglycoside Ototoxicity
Guan, Min-Xin
Volta Review, v105 n3 p211-227 2005
The mitochondrial DNA (mtDNA) 12S rRNA is a hot spot for mutations associated with both aminoglycoside-induced and nonsyndromic hearing loss. Of those, the homoplasmic A1555G and C1494T mutations at a highly conserved decoding region of the 12S rRNA have been associated with hearing loss. These two mutations account for a significant number of cases of aminoglycoside ototoxicity. The A1555G or C1494T mutation is expected to form novel 1494C-G1555 or 1494U-A1555 base-pair at the highly conserved A-site of 12S rRNA. These transitions make the secondary structure of this RNA more closely resemble the corresponding region of bacterial 16S rRNA. Thus, the new U-A or G-C pair in 12S rRNA created by the C1494T or A1555G transition facilitates the binding of aminoglycosides, thereby accounting for the fact that the exposure to aminoglycosides can induce or worsen hearing loss in individuals carrying these mutations. Biochemical characterization demonstrated an impairment of mitochondrial protein synthesis and subsequent defects in respiration in cells carrying the C1494T or A1555G mutation. Furthermore, the growth defect and impairment of mitochondrial translation in DMEM medium in the presence of high concentration of paromomycin or neomycin were observed in cell lines carrying the A1555G or C1494T mutations as compared to the average rate in control cell lines. These observations provide the direct genetic and biochemical evidence that the A1555G or C1494T mutation is a pathogenic mtDNA mutation associated with aminoglycoside-induced and nonsyndromic hearing loss. Therefore, these data provide valuable information and technology to predict: (1) which individuals are at risk for ototoxicity; (2) to improve the safety of aminoglycoside antibiotic therapy; and (3) eventually to decrease the incidence of deafness.
Alexander Graham Bell Association for the Deaf and Hard of Hearing. 3417 Volta Place NW, Washington, DC 20007. Tel: 202-337-5220; Fax: 202-337-8314; e-mail: periodicals@agbell.org; Web site: http://www.agbell.org
Publication Type: Journal Articles; Reports - Evaluative
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A