| 30%of the information obtained from the outside world by Human beings is from their hearing, and the loss of the hearing can seriously affect people’s life qualities. The results found in Second National Sample Survey on Disability in2006show that among the800,000to1,2million newborns disabilities, hearing disability is the most common and serious one. In China, there are more than27.8million hearing-impaired patients, accounting for33.5%of the82.96million people with disabilities, and it is the first of all types of disabilities. There are about800,0000-6-year-old hearing-impaired children among the hearing disabilities. And the newborns are up to30,000. If it plus late-onset deafness (post-lingual deafness) and drug-induced deafness patients, an annual increase of hearing-impaired children is up to more than60,000. Dumb caused by deafness not only seriously affect children’s intellectual and emotional communication, but also lead to the social barriers to participation and labor defects, which gives a heavy burden to the society and family. Of all the reasons of causing deafness, inherited hearing impairment is the main cause, which accounts for65%. for an annual increase of the new population, of which at least half the children was due to genetic defect of the cause, which can be caused by a single gene mutation or different gene composite mutations, can also be made by environmental factors, or both the genes and environment common function. A large amount of researches at home and abroad show that the common genetic deafness caused by a few hot spots of genetic mutations, such as GJB2, SLC26A4, mtDNA12S rRNA,GJB3and so on, that also provided theoretical basis for us to undertake large-scale genetic screening and diagnostic of deaf. And GJB2gene is the most common deafness genes which mainly causes congenital non-syndromic deafness, the majority are autosomal recessive mode of inheritance. It has been reported that GJB235delG、GJB2235delC、GJB2176del16、GJB2299delAT are the most common four major mutation hot spots among the deafness population. Deeper research on the distribution of the deafness population caused by GJB2genes has a great influence on the scientific guidance to the marriage of genetic deafness crowd and reducing the birth rate of hearing-impaired children. Objectives:At present, deaf students as well as outpatient patients are the main object of home and abroad study, and there is no systematic study on the hearing impaired certified hearing-impaired patients. The study aims to explore the molecular diagnostic significance of GJB2gene hotspot mutation in the hearing disabled populations in parts of Beijing. According to the genetic testing of6491deafness disabled patients with deafness deformity card in Beijing provided by The disabled association organization of Beijing, and selected objects are278severe non-syndrome deafness people in Yangzhou city, Jiangsu province. we analyzed frequency of GJB2gene hotspot mutation GJB235delG、JB2235delC、GJB2176del16、GJB2299delAT in order to achieve a preliminary understanding of molecular epidemiology characteristics in GJB2genes hot-spot mutations related to enlarged vestibular aqueduct conduit among Beijing area deafness disabled people, to achieve the purpose of service and clinical guidelines, and to provide the scientific help to matrimony and healthy birth of this group.Methods:The genomic DNA of the deafness disabilities as a template, the deafness gene mutations were distinguished by genechip, which is detection of nine hot-spot mutations in common genechip,(including:GJB235delG、GJB2235delC、GJB2176del16、GJB2299delAT、GJB3538C>T, SLC26A42168A>G、SLC26A4IVS7-2A<G、mtl2SrRNA1555A>G and1494C>T.) To selective examine Beijing area6491patients with deaf deformity card, including1958cases in Chaoyang,1062cases in Dongcheng area,2008cases in Fangshan area,833cases in Haidian area,629cases in Tongzhou area,278cases in Yangzhou area. The genomic DNA sample were extracted from blood, which from the deafness disabilities for3-5ml, and detected with the genomic DNA by the kit. For the purpose of PCR amplification, hybrid, and washing, read the result by the chip interpretation system. Analyzed the frequency and molecular epidemiological characteristics of GJB2genes in deaf hot-spot mutations GJB235delG, GJB2235delC、GJB2176del16、GJB2299delAT by the result.Results:Through this research, it has been found that among the two area deafness disabilities detected this time, The number of GJB2235delC、GJB2176del16、GJB2299delAT mutations carrying GJB2genes are totally572cases, total positive detection rate was8.82%(572/6491),total diagnose rate4.45%(289/6491). There were91.18%(5919/6491) deafness disabled persons not detected GJB2gene hot-spot mutations. The study also found that18cases deafness disabilities carrying GJB2meanwhile other gene chip hot gene mutations, of which1 case carrying GJB2homozygous mutation and GJB3heterozygous mutation, SLC26A4heterozygous mutation at the same time, from Dongcheng area;1case carrying GJB2homozygous mutation and SLC26A4heterozygous mutation at the same time, from Fangshan area;1case carrying GJB2double heterozygous mutation and SLC26A4heterozygous mutation from Fangshan area.4cases carrying GJB2heterozygous mutation and SLC26A4homozygous mutation,2, from Chaoyang area,1from Fangshan area and1from Tongzhou area.1case carrying GJB2heterozygous mutation and SLC26A4double mutation from Chaoyang area.7cases carrying GJB2heterozygous mutation and SLC26A4heterozygous mutation,4from Chaoyang area;1from Fangshan area;2from Haidian area;3cases carrying GJB2heterozygous mutation and mitochondrial homogeneous12SrRNA1555A> G mutation,2from Chaoyang area;1from Haidian area.Conclusions:1、Among the6491cases of disabled persons in deaf, through the GJB2gene mutations35delG、235delC、176del16、299delAT a test, we can determine the gene pathogenic molecular diagnostics accounts4.45%(289/6491)of the overall.2、In the deaf community holder in Beijing area, the detection rate of GJB2gene hot-spot mutations were lower than our clinic patients with deafness in PLA General Hospital. It May be related to the following factors:This study only test for GJB2gene hot-spot mutations but without all the sequence analysis; Part of the deafness disabled persons with card holder were not congenital deafness, such as noise induced hearing loss, presbycusis, knock deafness, drug-induced hearing loss, whose incidence and GJB2gene hot-spot mutations has poor association.3、The development of the subject help to understand the distribution of GJB2gene hot-spot mutations in Beijing area, clear diagnosis or guide further diagnosis for the deafness disabled people at the molecular level, and has certain directive significance of mating and fertility in the patients with positive GJB235delG、GJB2235delC、GJB2176del16、GJB2299delAT mutations.4、By etiologically diagnosis them from the perspective of molecular genetics, we found that the deaf patients in Yangzhou are found a higher incidence of genetic deafness in GJB2. It is worth applying the deafness gene diagnostic techniques into rapid diagnostic screening the cause of patients’ deafness. |
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