OBJECTIVETo identify secondary mutations associated with deafness in a Chinese family affected with deafness.

METHODSThe family has been subjected to clinical and molecular analyses, in addition with measurement of reactive oxygen species and doubling time after establishment of immortalized lymphocyte cell lines.

RESULTSThe results showed that the hearing loss level and audiometric configuration were discrepant among the family members with maternally transmitted hearing loss. The penetrance of hearing loss in this family was respectively 66.7% and 44.4% when aminoglycoside-induced hearing loss was included or excluded. Analysis of whole mitochondrial genome has found 33 variants as previously reported polymorphisms, except for a 12s rRNA A1555G mutation and a tRNA(Thr)T15943C mutation. Haplotype evolutionary tree has verified that this family belonged to East-Asian haplogroup F. 15943 position was located on the T-stem of the tRNA(Thr), which has destroyed the extremely conserved T-A base pair when T changed to C at this position. However, functional experiments indicated that the population doubling time in special galactose and glucose were longer, whilst the level of reactive oxygen species has increased. Compared with the control cell line groups and a family only carrying the 12s rRNA A1555G mutation, all of the three groups belonged to the same haplogroup.

CONCLUSIONMitochondrial tRNA(Thr)T15943C mutation may act as a potential modifying factor and interact with 12s rRNA A1555G mutation, and thereby enhance the penetrance and expression of deafness.