简介：Eachcomponentofthehumanearperformsaspecificfunctioninhearing.Theactualprocessofsoundtransductiontakesplaceintheauditoryportionoftheinnerear,thefluid-filledcochlea.Inthecochlea,thesensitivityandefficiencyofsensoryapparatustoconvertmechanicalenergyintoneuralactivity,largelydependsonthefluidicandionicenvironment.Inthelateralwallofcochlea,thesecretoryepitheliumstriavascularisplaysanimportantroleinthemaintenanceoffluidicandionichomeostasis.Avarietyofgenemutationsdisturbsthecochlearhomeostasisandsubsequentlyleadstohearingimpairment.Thereviewcoversseveralaspectsofcochlearhomeostasis,fromcochlearfluidandthefunctionalroleofstriavascularis,cochlearK+recyclinganditsmolecularsubstratestogeneticdeafnesswithabnormalcochlearhomeostasis.

简介：<正>OtosclerosiswasfirstdiscoveredbyValsalvain1704[1],andthetermwasfirstusedbyAntonvonTroltschin1872todifferentiatefromtympanosclerosis[2].Normallytheoticcystinhumanremainsstationaryafterfulldevelopmentandcontainsnovisibleactivatedosteoblastsor

简介：ObjectiveTounderstandthegeneticloadintheChinesepopulationforimprovementindiagnosis,preventionandrehabilitationofdeafness.MethodsDNAsamples,immortalizedcelllinesaswellasdetailedclinicalandaudiometricdatawerecollectedthroughanationalgeneticresourcescollectingnetwork.Twoconventionalgeneticapproacheswereusedinthestudies.LinkageanalysisinXchromosomeandautosomeswithmicrosatellitemarkerswereperformedinlargefamiliesforgenemappingandpositionalcloningofnovelgenes.CandidategeneapproachwasusedforscreeningthemtDNA12SrRNA,GJB2andSLC26A4mutationsinpopulation-basedsamples.ResultsAtotalof2,572Chinesehearinglossfamiliesorsporadiccaseswerecharacterizedinthereportedstudies,includingsevenX-linked,oneY-linked,28largeandmultiplexautosomaldominanthearinglossfamilies,607simplexautosomalrecessivehereditaryhearinglossfamilies,100mitochondrialinheritancefamilies,147GJB2inducedhearinglosscases,230caseswithenlargedvestibularaqueduct(EVA)syndrome,169sporadiccaseswithauditoryneuropathy,and1,283sporadicsensorineuralhearinglosscases.Throughlinkageanalysisorsequenceanalysis,twoX-linkedfamilieswerefoundtransmittingtwonovelmutationsinthePOU3F4gene,whileanotherX-linkedfamilywasmappedontoanovellocus,nominatedasAUNX1(auditoryneuropathy,X-linkedlocus1).TheonlyY-linkedfamilywasmappedontotheDFNY1locus(Y-linkedlocus1,DFNY1).Eightofthe28autosomaldominantfamilieswerelinkedtovariousautosomalloci.Inpopulationgeneticsstudies,2,567familialcasesandsporadicpatientsweresubjectedtomutationscreeningforthreecommonhearinglossgenes:mtDNA12SrRNA1555G,GJB2andSLC26A4.TheauditoryneuropathycasesinoursampleswerescreenedforOTOFgenemutations.ConclusionsThesedatashowthattheChinesepopulationhasageneticloadonhereditaryhearingloss.Establishingpersonalizedsurveillanceandpreventionmodelsforhearing

简介：MutationsintheGJB2genearethemostfrequentlyfoundmutationsinpatientswithnonsyndromichearingimpairment.However,themutationspectrumandprevalenceofmutationsvaryamongdifferentethnicgroups.Everyyear,30,000babiesarebornwithcongenitalhearingimpairmentinChina.Inordertoprovideappropriategenetictestingandcounselingtothefamily,weinvestigatedthemolecularetiologyofnonsyndromicdeafnessin135unrelatedschoolchildrenattendingChifengMunicipalSpecialEducationSchoolinInnerMongolia,China.ThecodingexonoftheGJB2genewasPCRamplifiedandsequenced.Inaddition,the12SrRNAgeneandtRNAser(UCN)ofmitochondrialgenomewerescreenedformutationsresponsibleforhearingimpairment.SixtyfourGJB2mutantalleles,including60confirmedpathogenicallelesand4unclassifiedvariants,wereidentifiedin31.1%(42/135)ofthesubjects.Twentytwosubjectscarriedtwopathogenicmutationsand20subjectscarriedonemutantallele,includingonesubjectwithoneautosomaldominantmutation.The235delCwasthemostcommonmutationaccountingfor65.6%(42/64)GJB2mutantalleles.WhencomparedtootherAsianpopulations,oursubjectcohorthadhigherfrequencyof235delCmutationthantheJapanesepopulation.TheGJB2mutantallelesaccountfor23.7%(64/270)ofallchromosomesresponsiblefornonsyndromichearingimpairment.Testingofthe4mostprevalentdeleteriousframeshiftmutations(235delC,299_300delAT,176_191del16,and560_605ins46)inthiscohortdetected90%ofallGJB2mutantalleles.TheseresultsdemonstratethateffectivegenetictestingoftheGJB2geneforpatientsandfamilieswithnonsyndromichearingimpairmentispossibleintheChinesepopulation.Sincethemostcommon309kbGJB6deletionisnotdetectedandonlyone1555A>GmutationinmitochondrialDNAisdetectedinourpatients,investigationofmutationsinothernucleargenesand/orenvironmentalfactorsresponsiblefornonsyndromichearingimpairmentintheChinesepopulationis

简介：Hearingloss(HL)isthemostcommonsensorydisorder,affectingallagegroups,ethnicities,andgen-ders.AccordingtoWorldHealthOrganization(WHO)estimatesin2005,278millionpeopleworldwidehavemoderatetoprofoundHLinbothears.Resultsofthe2002NationalHealthInterviewSurveyindicatethatnearly31millionofallnon-institutionalizedadults(aged18andover)intheUnitedStateshavetroublehearing.Epidemiologicalstudieshaveestimatedthatapproximately50%ofprofoundHLcanbeattributedtogeneticcauses.Withover60genesimplicatedinnonsyndromichearingloss,itisalsoanextremelyhet-erogeneoustrait.Recentprogressinidentifyinggenesresponsibleforhearinglossenablesotolaryngologistsandotherclinicianstoapplymoleculardiagnosisbygenetictesting.Theadventofthe$1000genomehasthepotentialtorevolutionizetheidentificationofgenesandtheirmutationsunderlyinggeneticdisorders.ThisisespeciallytrueforextremelyheterogeneousMendelianconditionssuchasdeafness,wherethemuta-tion,andindeedthegene,maybeprivate.Therecenttechnologicaladvancesintarget-enrichmentmethodsandnextgenerationsequencingofferauniqueopportunitytobreakthroughthebarriersoflimitationsim-posedbygenearrays.Theseapproachesnowallowforthecompleteanalysisofallknowndeafness-causinggenesandwillresultinanewwaveofdiscoveriesoftheremaininggenesforMendeliandisorders.Thisre-viewfocusesondescribinggenotype-phenotypecorrelationsofthemostfrequentgenesincludingGJB2,whichisresponsibleformorethanhalfofcases,followedbyothercommongenesandondiscussingtheim-pactofgenomicadvancesforcomprehensivegenetictestingandgenediscoveryinhereditaryhearingloss.

简介：Weinvestigatedthepharmacokineticsofcaroverineintheperilymph,cerebrospinalfluidandplasmaaftersystemicandlocaladministrationsinguineapigsbyusinghigh-performanceliquidchromatography.Auditorybrainstemresponsesweremeasuredtoevaluateauditoryfunctionaleffect.Theresultsshowedthatlocalapplicationwasabothsafeandefficientmethod.Wefurtherreviewedliteratureandpinpointedthattheroundwindowiseffectivelylocaldrugdeliverymeansforfutureinnereartreatment.

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