SUSCEPTIBILITY MUTATIONS IN THE MITOCHONDRIAL SMALL RIBOSOMAL-RNA GENE IN AMINOGLYCOSIDE INDUCED DEAFNESS

Aminoglycoside induced deafness has been linked recently to a predispo sing homoplasmic mutation in the 3' end of the small ribosomal RNA (rR NA) gene of the human mitochondria (1555 A-->G) that makes the mitocho ndrial rRNA structurally more similar to its bacterial counterpart. Th is mitochondrial DNA mutation was consistently found in families in wh ich the susceptibility to develop ototoxic deafness was inherited thro ugh the maternal lineage, However, the 1555 A-->G mutation was rarely found in sporadic patients in China, where a significant proportion of the population has been exposed to aminoglycosides, To further charac terize the mutations predisposing to aminoglycoside ototoxicity, we an alysed the 12S rRNA gene in 35 Chinese sporadic patients without the 1 555 A-->G mutation, Using single stranded conformational polymorphism (SSCP) analysis, heteroduplex (HD) analysis, sequencing, and allele sp ecific oligonucleotide hybridization, we found three out of 35 sporadi c patients with unique sequence changes in the 12S rRNA gene, Two of t he patients had homoplasmic mutations, One patient displayed localized heteroplasmy around nt 961, with an absence of the thymidine at this position and different populations of mitochondrial DNA with varying n umbers of inserted cytosines, The description of these putative suscep tibility mutations, in particular the heteroplasmic mutation around nt 961, provides further support for the important role of the mitochond rial 12S rRNA in genetic predisposition to aminoglycoside induced otot oxic deafness,