Epidemiological Investigation Of SLC26A4Gene Hot-spot Mutation For Enlarged Vestibular Aqueduct In Deafness Disabled Populations In Beijing Of China

Deafness, as one of the most common defect, serious influence humancognition and communication, which brings a great inconvenienceto these patients' life and study. In the quality of life increased today,deafness gained more and more attention. In our country,according to thesecond national handicapped person sampling survey results calculated,thehearing disabilities (including multiple disabilities) were27.8million, ofwhich simply listening of20.04million were disabled, accounting for24.16%of the total disability population, by April1,2006. So many patients with deafand the number was growing, every year new hearing and language disordersnearly80000people, for an annual increase of nearly30000people, of whichat least half the children was due to genetic defect of the cause, which can becaused by a single gene mutation or different gene composite mutations, canalso be made by environmental factors, or both the genes and environmentcommon function. A large amount of researches at home and abroad show thatthe common genetic deafness caused by a few hot spots of genetic mutations,such as GJB2, SLC26A4, mtDNA12S rRNA and so on, that also provided theoretical basis for us to undertake large-scale genetic screening anddiagnostic of deaf. The enlarged vestibular aqueduct related to SLC26A4geneclosely, is a kind of autosomal recessive genetic disease, and Enlargedvestibular aqueduct is the most common inner ear malformation. Therefore,mastering the distribution characteristics of the hot spot mutation in theSLC26A4gene in the group of deaf people with disabilities, as well as theguidance of the marriage of the science of high-risk hereditary deafness crowdof great significance.Objectives:To preliminary discuss the significance of molecular diagnosis of SLC26A4gene hot-spot mutations among the deafness disabledpeople in Beijing. Through the genetic tests of6247deafness disabled patientswith deafness deformity card in Beijing provided by The disabled associationorganization of Beijing, We analyzed the frequency of SLC26A4genes in deafhot-spot mutations IVS7-2A> G and2168A> G among Beijing disabledpeople in order to achieve a preliminary understanding of molecularepidemiology characteristics in SLC26A4genes hot-spot mutations related toenlarged vestibular aqueduct conduit among Beijing area deafness disabledpeople, to achieve the purpose of service and clinical guidelines, and toprovide the scientific help to matrimony and healthy birth of this group.Mothods: Working principle of the gene chip: The DNA of the deafnessdisabilities as a template, the deafness gene mutations were distinguished bygenechip. which is detection of nine hot-spot mutations in commongenechip,including: GJB235delG,GJB2235delC,GJB2176del16,GJB2299delAT,GJB3538C>T,SLC26A42168A>G,SLC26A4IVS7-2A>G,mt12SrRNA1555A>G and1494C>T.To selective examine Beijing area6247patients with deaf deformity card, including1261cases in yanqing,1731cases in huairou area,1542cases in Men-tou vallely area,635cases inhaidian area,554cases in fangshan area,524cases in miyun area, the male3398cases, female2849cases. The genomic DNA sample were extractedfrom blood,which from the deafness disabilities for3-5ml,and detected withthe genomic DNA by the kit. For the purpose of PCR amplification,hybrid,and washing, read the result by the chip interpretation system.Analyzedthe frequency and molecular epidemiological characteristics of SLC26A4genes in deaf hot-spot mutations IVS7-2A> G and2168A> G by the result.Results:Through this research found that among the6247Beijingdeafness disabilities detected this time, The number of IVS7-2A> G and2168A> G mutations carrying SLC26A4genes total amount177cases, totalpositive detection rate was2.83%(177/6247),total diagnose rate0.46%(41/6247), namely patients carrying SLC26A4single allele mutant was2.83%(177/6247), patients carrying double mutant allele accounted for0.46% (41/6247). we detected218SLC26A4mutant alleles, mutant allele frequency(the numbers of mutation alleles/total alleles) was1.74%(218/12494). Therewere97.17%(6070/6247) deafness disabled persons not detected SLC26A4gene hot-spot mutations. The study also found that4cases deafnessdisabilities carrying SLC26A4meanwhile other gene chip hot gene mutations,of which1case carrying GJB3538C>T heterozygous mutation and SLC26A4IVS7-2A>G heterozygous mutation at the same time, from Huairou area;1case carrying GJB2299delAT heterozygous mutation and SLC26A4IVS7-2A>G heterozygous mutation at the same time, from Haidian area;1casecarrying GJB2235delC heterozygous mutation and SLC26A42168A>Gheterozygous mutation at the same time, from Yanqing area;1case carryingGJB2235delC homozygous mutant and SLC26A42168A>G heterozygousmutation at the same time, from Yanqing area.Conclusions:1,Among the6247cases of disabled persons in deaf,through the SLC26A4gene mutations IVS7-2A>Gand2168A test, we candetermine the molecular diagnosis acount0.46%(41/6247)of the overall.2,Inthe deaf community holder in Beijing area, the detection rate of SLC26A4gene hot-spot mutations were lower than our clinic patients with deafness.May be related to the following factors: This study only test for SLC26A4gene hot-spot mutations but without all the sequence analysis; Part of thedeafness disabled persons with card holder were not congenital deafness, suchas presbycusis, occupational noise-induced hearing loss, deafnessknock,whose incidence and SLC26A4gene hot-spot mutations has poorassociation.3,The development of the subject help to understand thedistribution of SLC26A4gene hot-spot mutations closely related enlargedvestibular aqueduct syndrome among the disabled people in Beijing area, cleardiagnosis or guide further diagnosis for the deafness disabled people at themolecular level, and And has certain directive significance of mating andfertility in the patients with positive IVS7-2A>G and2168A>G mutations.