title: 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.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland. marydz@man.poznan.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.forename: Karolina
authors.initials: K
authors.lastname: Cywińska
authors.forename: Maciej
authors.initials: M
authors.lastname: Wróbel
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pollak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Gawęcki
authors.forename: Irena
authors.initials: I
authors.lastname: Wojsyk-Banaszak
authors.forename: Urszula
authors.initials: U
authors.lastname: Lechowicz
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Mueller-Malesińska
authors.forename: Monika
authors.initials: M
authors.lastname: Ołdak
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.forename: Henryk
authors.initials: H
authors.lastname: Skarżyński
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szyfter
authors.forename: Witold
authors.initials: W
authors.lastname: Szyfter
mesh_terms: D000617:Aminoglycosides / Q000009:adverse effects*; D001299:Audiometry; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011044:Poland; D012362:RNA, Transfer, Ser / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012362:RNA, Transfer, Ser; D003576:Electron Transport Complex IV