The contribution of the mitochondrial COI/tRNA(Ser(UCN)) gene mutations to non-syndromic and aminoglycoside-induced hearing loss in Polish patients.

Abstract

Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed the systematic mutation screening of the COI/tRNA(Ser(UCN)) genes in 250 unrelated Polish subjects with hearing impairment. Three different homoplasmic sequence variants were identified, including one common polymorphism m.7476 C>T in tRNA(Ser(UCN)) and two mutations, m.7444 G>A and m.7445 A>G localized in the COI/precursor of tRNA(Ser(UCN)). The incidence of m.7444 G>A substitution was estimated at 1.6% (4/250), however variable penetrance of hearing loss, age of onset and hearing thresholds among m.7444 G>A carriers was observed. Two subjects had the positive history of aminoglycoside exposure and one of them harbored both m.7444 G>A and 12S rRNA m.1555 A>G mutations. Those suggest that m.7444 G>A itself is not sufficient to produce a clinical phenotype and additional modifier factors are required for pathogenic manifestation of m.7444 G>A substitution. Moreover, we have described the first Polish family with non-syndromic hearing loss, harboring m.7445 A>G mutation. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing impairment was included, and 8% when ototoxic effect was excluded. This finding strongly suggests the possible role of m.7445 A>G in susceptibility to aminoglycoside induced-hearing loss.

• Authors: Małgorzata Rydzanicz, Karolina Cywińska, Maciej Wróbel, Agnieszka Pollak, Wojciech Gawęcki, Irena Wojsyk-Banaszak, Urszula Lechowicz, Małgorzata Mueller-Malesińska, Monika Ołdak, Rafał Płoski, Henryk Skarżyński, Krzysztof Szyfter, Witold Szyfter
• Journal: Molecular genetics and metabolism (Mol Genet Metab) 2011 Sep-Oct Vol. 104 Issue 1-2 Pg. 153-9 ISSN: 1096-7206 [Electronic] United States
• PMID: 21621438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Aminoglycosides
• DNA, Mitochondrial
• RNA, Transfer, Ser
• Electron Transport Complex IV

Topics

• Aminoglycosides (adverse effects)
• Audiometry
• Base Sequence
• Child
• Child, Preschool
• DNA Mutational Analysis
• DNA, Mitochondrial (genetics)
• Electron Transport Complex IV (genetics)
• Female
• Hearing Loss, Sensorineural (chemically induced, genetics)
• Humans
• Infant
• Male
• Mitochondria (enzymology, genetics)
• Molecular Sequence Data
• Mutation (genetics)
• Pedigree
• Poland
• RNA, Transfer, Ser (genetics)