Identification of a mitochondrial 12S rRNA A1555G mutation causing aminoglycoside-induced deafness in a large Thai family

Background Hearing loss is among the most frequent sensory disorders. Preventable causes include medications given to genetically susceptible individuals. Several families around the world with an A1555G mitochondrial mutation who became profoundly deaf after receiving aminoglycosides have been described. However, none has been reported in Thailand. Objectives To identify the cause of hearing loss of a large Thai family with 11 members who reportedly turned deaf after receiving antibiotics. Methods We obtained blood samples from 5 members; 4 of whom had hearing loss. Mutation analyses were performed using molecular techniques including polymerase chain reaction, Sanger sequencing, and restriction fragment length polymorphism. Results All 4 affected members were found to harbor the same A1555G mitochondrial mutation, while the unaffected had only the wild-type A. Conclusions We have identified the mitochondrial mutation leading to aminoglycoside-induced hearing loss in a Thai population. Raising awareness for medical practitioners of this genetic susceptibility in Thailand is warranted. Avoidance of certain medications in these individuals would prevent this acquired permanent hearing loss.

Mosaicism of Mitochondrial Genetic Variation in Atherosclerotic Lesions of the Human Aorta

Objective.The aim of the present study was an analysis of heteroplasmy level in mitochondrial mutations 652delG, A1555G, C3256T, T3336C, 652insG, C5178A, G12315A, G13513A, G14459A, G14846A, and G15059A in normal and affected by atherosclerosis segments of morphologically mapped aortic walls.Methods.We investigated the 265 normal and atherosclerotic tissue sections of 5 human aortas. Intima of every aorta was divided according to morphological characteristics into segments with different types of atherosclerotic lesions: fibrous plaque, lipofibrous plaque, primary atherosclerotic lesion (fatty streak and fatty infiltration), and normal intima from human aorta. PCR-fragments were analyzed by a new original method developed in our laboratory on the basis of pyrosequence technology.Results.According to the obtained data, mutations G12315A and G14459A are significantly associated with total and primary atherosclerotic lesions of intimal segments and lipofibrous plaques (P≤0.01andP≤0.05, accordingly). Mutation C5178A is significantly associated with fibrous plaques and total atherosclerotic lesions(P≤0.01). A1555G mutation shows an antiatherosclerotic effect in primary lesion in lipofibrous plaques(P≤0.05). Meanwhile, G14846A mutation is antiatherogenic for lipofibrous plaques(P≤0.05).Conclusion.Therefore, mutations C5178A, G14459A, G12315A, A1555G, and G14846A were found to be associated with atherosclerotic lesions.