简介：Microphthalmia-associatedtranscriptionfactor(MITF)controlsmelanocytesurvivalanddifferentiationthroughdirectlyregulatingtheexpressionofthetyrosinase(TYR)andtyrosinase-relatedproteins1and2(TYRP1andTYRP2)genes.MITFmutationshavebeenreportedtoresultinanabnormalmelanocytedevel-opmentandleadtoWaardenburgsyndrometype2(WS2),characterizedbyvariabledegreesofsensorineu-ralhearinglossandpatchyregionaldistributionofhypopigmentation.Recently,MITFwasalsoindicatedasacausativegeneforamoreseveresyndrome,theTietzSyndrome(TS),characterizedbygeneralizedhy-popigmentationandcompletehearingloss.However,fewfunctionalstudieshavebeenperformedtocom-parethediseases-causingmutations.Here,weanalyzedtheinvitroactivityoftworecentidentifiedWS2-as-sociatedmutation(p.R217Iandp.T192fsX18)andoneTS-associatedmutationp.N210K.TheR217IMITFretainedpartialactivity,normalDNA-bindingabilityandnucleardistribution,whereastheT192fsX18MITFfailedtoactivateTYRpromoterduetolossofDNA-bindingactivity,andaberrantsubcellularlocalization.TheaberrantsubcellularlocalizationofT192fsX18MITFmaybecausedbydeletionofaputativenuclearlocalizationsignal(NLS)ataa213-218(ERRRRF).Indeed,MITFwithdeletionoftheNLSfragmentfailedtotranslocateintothenucleusandactivatedtheTYRpromoter.TaggingthisNLStoGFPpromotedthegreenfluorescenceprotein(GFP)translocatedintothenucleus.ThesurprisingfindingofourstudyisthataTS-as-sociatedMITFmutation,N210K,showedcomparableinvitroactivityasWT.Thus,thepossibleinvolve-mentofMITFinTSanditsunderlyingmechanismsstillneedfurtherinvestigation.

简介：Waardenburgsyndromeisararediseasecharacterizedbysensorineuraldeafnessinassociationwithpigmentarydefects.Dependingonadditionalsymptoms,WShavebeenclassifiedintofourtypes.Waardenburgsyndrometype4,alsocalledasWaardenburgShahSyndromeisaveryrarecongenitaldisorderwithastoundingvariableclinicalexpression,characterizedbypigmentaryabnormalitiesofthehair(Awhiteforelockofhair,prematuregraying)andpigmentarychangesoftheirissuchasheterochromiaorhomochromiairides,sensorineuraldeafnessandHirschsprungdisease.ThreegeneshavebeenbestowedsofarinconsociationwithEDNRB,EDN3,andSOX10genes.ThepatternofinheritanceismultifariouswiththeSOX10mutationaffiliationwithautosomaldominantinheritancewhereastheEDNRBandEDN3genesarepasseddowninanautosomallyrecessivepattern.

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简介：AlportsyndromeisanX-linkedsyndromethatresultsinnephritis,renalfailure,sensorineuralhearingloss,andeyedeficits.Asaresultofsensorineuralhearingloss,theseindividualsarelikelytoexperiencedifficultiesintheareaofspeechandlanguage.Whilestudiesinthepasthaveexaminedthespeechandlanguagecharacteristicsofchildrenwithsyndromicsensorineuralhearingloss,toourknowledgetherearenopreviousstudiestohavedocumentedthespeechandlanguagecharacteristicsofthesechildrenonalong-termbasis.Thecurrentstudyaddressesthislimitationbyreportingspeech,language,hearing,andfunctionoftwinbrotherswithX-linkedAlportsyndromeacrossaseven-yearperiod.Informationwascollectedbyexaminingthemedicalrecordsoftheparticipantsaswellasthroughaverbalinterviewwiththeparticipants'guardian.Resultsrevealedthattheparticipants'hearingabilitiesgraduallydeterioratedovertheseven-yearperiodwhichaffectedtheirspeechandlanguagedevelopmentaswell.Thekidneyfunctiontestsrevealedsignificantpresenceofhematuria(bloodintheurine)aswellasproteinuria(proteinintheurine)suggestingchronickidneydysfunction.Thislongitudinalstudydemonstratesthefunctionalrelationshipbetweenthekidneysandthecochlea,althoughtheyappeartobeindependentofoneanother.AsindividualswithAlportsyndromeexhibitsystemiccomplications,interdisciplinarycollaborationisessentialamonghealthcareprovidersincludingaudiologists,speech-languagepathologists,nephrologists,andophthalmologisttopromoteevidence-basedpractice.

简介：Thestudyreportsacaseofa5-year-oldChinesegirldiagnosedwithKabukimake-upSyndrome(KMS).ThepatientshowedclassicKMSappearance:widelyseparatedeyes,ectropionoflateralone-thirdlowereyelids,flatnasaltip,andprominentears.Auditoryfeaturesinthisindividualincludedbilateralseveresensorineuralhearinglossandlackof40HzAERPresponsesidentifiedatIyearofage.Theindividualreceivedcochlearimplant(CI)intheleftearwhen5yearsold.andrehabilitationafterCItreatmentwere3inspeechintelligibilityand5inauditoryperformance.Thus,ourfindingssuggestthatcochlearimplantmaybehelpfultorestorehearingforindividualswithKabukisyndrome.