| Based on the massive clinical and experimental research, the mutations atpositions1555and1494in the12S rRNA gene account for super-sensitivity toaminoglycosides, which means the administration of normal dosage or lessaminoglycosides can induce or worsen deafness in the patients with suchmutations. But several individuals with such mutations do show non-sensitivity toaminoglycosides. To study the molecular genetics and cell functions ofnon-sensitivity to aminoglycosides in this family and to analyses the molecularmechanism.We collected some data of inherit deafness and found a family withmaternally transmitted aminoglycoside-induced and non-syndromic deafness inHebei Province. In the absence of aminoglycosides, some matrilineal relatives inthis family exhibited late-onset/progressive deafness, with a wide range ofseverity and age. Clinical data reveal that the administration of aminoglycosidescan induce deafness in mostly matrilineal relatives. But one of the matrilinealrelatives with history of normal dosage of aminoglycosides administrationmaintained normal hearing level.Sequence analysis of mitochondrial DNA in this pedigree identified ahomoplastic A-to-G transition at position1555（A1555G） in the12S rRNA gene.There was a variation found in the MTO1gene:7420200074202001insG and74202003delG, which indicated that MTO1gene might have been the nuclear modified gene in this family. There was no significant mutation in the TRMUgene. Exposure to a high concentration of aminoglycosides caused an increase indoubling time in lymphoblastoid cell lines derived from one symptomatic and oneasymptomatic individuals in this family carrying the A1555G mutation whencompared to two control cell lines.These results suggest that the nuclear background plays a role in theaminoglycoside ototoxicity and in the development of the deafness phenotypeassociated with the A1555G mutation in the mitochondrial12S rRNA gene. |
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