Mutation Analysis For The Mitochondrial DNA In A Pedigree With Aminoglycoside Antibiotic Induced Deafness

Objective Application of the DNA microarray which is able to perform mutation detection of 2 hot-spot mutations in one most common mitochondrial DNA gene simultaneously, including mitochondrial 12S rRNA(A1555G,C1494T),to detect the patients who were the family members of a pedigree with a maternally inherited aminoglycoside antibiotic-induced deafness,deaf students,and clinical patients.Screening and testing for this mutation are effective methods to prevent ototoxicity in A1555G carriers and their maternal family members.Methods Eigty-two non-syndromic hearing loss individuals were included in this study. Blood samples were obtained from 12 family members in a pedigree with a maternally inherited aminoglycoside antibiotic-induced deafness,and 70 sporadic non-syndromic deafness coming from Taiyuan School for the Deaf and our hospital. We collected peripheral blood 5ml and extracted DNA from the isolated leukocytes with phenol/chloroform method,then the mitochondrial DNA target fragments were amplified by polymerase chain reaction (PCR). Their genomic DNA samples were detected with the DNA microarray which is able to perform mutation detection of 2 hot-spot mutations in one most common pathologic mitochondrial DNA gene including mitochondrial 12SrRNA(A1555G,C1494T) simultaneously.Results In the 82 cases of samples,we extracted DNA 81cases successfully,including 12 cases of family members,61 cases of deaf school students and 8 clinical patients. The homoplasmic A1555G mutation was found in 7 individuals of 81 patients,and all the positive patients were coning from the drug-induced deafness pedigree. The C1494Tmutation did not appear in all cases.Conclusion Our results suggested that the mitochondrial DNA 1555G mutation may be one of major factors resulted in aminoglycoside antibiotic-induced deafness in this pedigree, and the 1555G carriers were mainly distributed in the pedigree with maternally inherited deafness.Additionally,this mutation can result in various grades of deafness.The deafness grades ranged from normal to profound. We identified the hereditary model of the pedigree was non-syndromic sensoneural hearing loss mitochondrial inheritance.