The Molecular Aetiology Study In Non-syndromic Hearing Impairment

Along with the accomplishing of Human Genome Project(HGP) and the arrivaling ot post-genomic era,It has already became the hot spot to discuss the molecular etiology ot hereditary deafness in the gene level.The otolaryngologists who are cooperate with the molecular genetists and the diologists in the global scope have broken many genes for hereditary hearing loss or impairment at the surprising speed.Up to present,74 genes with hearing have already discoved.It provides for us the exciting opportunities to discover the molecular hereditary mechanism of hearing loss or impairment in molecular level.At present,the related research work about the causative genes of hearing loss mainly includes two aspects,that is,on the one hand is to locate and clone new deafness genes and further to research the functions for these genes;on the other hand is to confirm the relevance among clinical manifestations and deaf genes by investigation of molecular epidemiology.Based on the second directions,our studies include two parts which are composed of two chapters as follows.The First Part:Investigation of 517 patients with hearing impairment in common genes related the deafness in the Northwest of ChinaThe molecular epidemiology basis of GJB2,SLC26A4 and mitochondrial DNA mutations for understanding the causative effects was investigated among a total number of 517 patients with hearing loss in the Northwest of China,who wre diagnosed as non-syndromic hearing impairment,severe or profound deafness.In the present study, pathologic mutations were identified in 111 cases,making up 21.47%(111/517).59 cases (11.47%) were found to have homozygous and compound heterozygosis mutation in GJB2 gene,23 cases(4.45%) were found to have homozygous and compound heterozygosis mutation in SLC26A4 gene,29 cases(5.61%) were found to carry mitochondrial DNA 12SrRNA A1555G mutation.We can further identify the frequency and the characteristic of the common deaf gene in the Northwest of China,and provid the reliable theory basis for develop the large-scale genetic screening in further.It also instruct the personalized hearing intervention measure for the deafness from the different causes.Meanwhile,these are effective in genetic counseling,the prenatal diagnosis and optimum methods of child-bearing and child-rearing.The Second Part:Investigation of TMC1 gene mutation in nonsyndromic hearing impairmentTo explore the clinical significance of screening the mutation of TMC1 gene in patient with hearing impairment in China,434 subjects were recruited from many deaf-mute schools and families,these subjects were verified to be negative at three common hearing loss loci(mtDNAA1555G,GJB2 and SLC26A4) and were defined as case group to be sought for additional genetic causes associated with TMC1 gene.In the control group,eighty-seven subjects with normal hearing were recruited from the same region to this study.Thirteen patients(two from two multiplex families and eleven from eleven simplex families) were detected with monoallelic mutations.We found that the two newly identified mutations(1713C＞T and IVS19+20G＞A) in Chinese patients were novel which not revealed from previous studies based on other ethnical populations,a synonymous SNP(45C＞T) was also identified in three patients and two health controls.Our analysis indicates that TMC1 mutations accounted for at least 3.0%(13/434) of nonsyndromic hearing loss cases in Chinese,and the identified two mutations might be unique to Chinese. TMC1 might is another gene which closely related to hereditary nonsyndromic hearing impairment in Chinese.