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

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/tRNASer(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 tRNASer(UCN) and two mutations, m.7444 G>A and m.7445 A>G localized in the COI/precursor of tRNASer(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.