Molecular Epidemiology And Mechanism Study Of Mitochondrial DNA A1555G Mutation In Hearing Impairment

Mitochondrial DNA (mtDNA) mutations have been found to be associated with sensorineural hearing loss. In particular, the mtDNA A1555G mutation has been shown to be a hot spot for aminoglycoside induced and non-syndromic hearing loss in different population from all over the world. In China, there are also many reports to reveal the pathogenesis of maternal inherited deaf families closely related to both A1555G mutaiton and administration of aminoglycoside antibiotics. But most of these studies focused on the families with unique maternal inherited pattern, which would ignore untypical families with only one or two deaf patients. A systematic and extended mtDNA A1555G mutation screening project has been initiated in both the large clinical population of Otology Clinic at the Chinese PLA General Hospital and a large deaf population from Deaf and Dumb school of different area in China. These results exhibit the significance of mitochondrial DNA A1555G mutation screening in large Chinese population and explore the molecular mechanism in non-syndromic hearing loss caused by mitochondrial DNA mutation.This study was composed of three parts below:Part I: The clinical data collection of patients with inherited hearing loss and the screening of mtDNA A1555G mutation inhearing impairment patients in ChinaWe collected clinical data of patients with inherited hearing loss from the outpatient department of the PLA General Hospital and the Deaf and Dumbschool of different area in China. In results, we collected the clinical data of 2993 patients during March 2003 and May 2006. All the samples were screened by a compact testing kit for mtDNA A1555G mutation. We found ninety six patients with mtDNAA1555G mutation.Part II: Preventive significance of mitochondrial DNA A1555Gmutation screening in large Chinese deaf populationTo analyze 71 pedigrees that all of these have an mtDNA A1555G mutation. One hundred and forty one matrilineal members suffered hearing loss while 898 matrilineal members were hearing normal. To find one A1555G carrier will alert more than 12 matrilineal relatives and guide prescription for these individuals. Maternal inherited deafness families were distributed widely in China. The detection of mtDNA A1555G mutation by the testing kit with low cost is needed and suitable in China for large scale screening and preventive testing before usage of aminoglycoside antibiotics.PartHI: The study of the molecular mechanism in non-syndromichearing loss caused by mitochondrial DNA mutation.To explore the molecular mechanism by sequencing in 75 normal students and 164 non-syndromic hearing loss patients in the mitochondrial DNA 12S rRNAj *t>xt a Ser (UCN)and tRNA gene.