Mechanism and Functional Research on Nuclear Modified Gene Associated with Maternally Inherited Aminoglycoside-Induced Deafness
Liu Ri-yuan
Liu Qi
Hao Qing-qing
Dong Si-qi
Xu Guang-yu
Zhao Hui
Abstract：Objective To study the molecular genetics and cell functions of non-sensitivity to aminoglycosides and to an-alyze the molecular mechanism in a family with maternally transmitted aminoglycoside-induced non-syndromic deafness. Methods A clinical,molecular,genetic and phylogenic analysis in this Chinese family was performed. Results Sequence analy-sis of mitochondrial DNA in this pedigree identified a homoplastic A-to-G transition at position 1555 (A1555G) in the 12S rRNA gene. Analysis of the complete mtDNA genome revealed that this family belonged to haplotype D5b1b and exhibited high penetrance in contrast with other reported families. There was a variation found in the MTO1 gene: 74202000_74202001insG and 74202003delG, indicating that the MTO1 gene may be the nuclear modified gene in this family. There was no significant mutation in the TRMU gene. Exposure to a high concentration of aminoglycosides caused an increase in dou-bling time in lymphoblastoid cell lines derived from one symptomatic individual in this family, while the doubling time of the cell lines from the asymptomatic individual didn’t increase. Conclusion These results suggest that the nuclear background plays a role in the aminoglycoside ototoxicity and in the development of the deafness phenotype associated with the A1555G mutation in the mitochondrial 12S rRNA gene.
Keywords：DeafnessMitochondrial DNAAminoglycosidesNuclear Modified Gene
Publication Date：2013-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 345-352 )