資源描述：
《Identification and Functional Characterization of CardiacTroponin I As a Novel Disease Gene in AutosomalDominant Dilated Cardiomyopathy心臟的識別與功能鑒定 肌鈣蛋白I作為Autosomal新的疾病基因 顯性擴張型心肌病》由會員上傳分享，免費在線閱讀，更多相關(guān)內(nèi)容在學術(shù)論文-天天文庫。
1、ClinicalResearchIdentificationandFunctionalCharacterizationofCardiacTroponinIAsaNovelDiseaseGeneinAutosomalDominantDilatedCardiomyopathySebastianCarballo,PaulRobinson,RobynOtway,DianeFatkin,JanD.H.Jongbloed,NicolaasdeJonge,EdwardBlair,J.PetervanTintelen,CharlesRedwood,HughWatkinsRati
2、onale:Idiopathicdilatedcardiomyopathy(DCM)isinheritedinapproximatelyonethirdofcases,usuallyasanautosomaldominanttrait.Morethan30locihavebeenidentified,severalofwhichencodesarcomericproteinswhichcanalsobemutatedtocausehypertrophiccardiomyopathy.Onecontractileproteingenewellknownasahyp
3、ertrophiccardiomyopathydiseasegene,butwithnoreportedmutationinautosomaldominantDCM,isTNNI3whichencodescardiactroponinI.Objective:TotestTNNI3asacandidategene,apanelof96probandswithDCMwasanalyzed.MethodsandResults:GenomicDNAwasisolatedandTNNI3exonsscreenedbyheteroduplexanalysis.Exonswi
4、thaberrantprofilesweresequencedandvariantsevaluatedbysegregationanalysisandstudyofnormalcontrols.Wereport2novelTNNI3missensemutations,Lys36GlnandAsn185Lys,eachassociatedwithsevereandearlyonsetfamilialDCM.Ofthe5mutationcarriers,cardiactransplantationwasrequiredin3,atages6,15,and242ye
5、ars.AnalysisofCaregulationofactin-tropomyosin–activatedmyosinATPasebytroponinrevealedthat2troponinreconstitutedwitheithermutanttroponinIgavelowermaximumATPaseratesandlowerCa2sensitivitythanwildtype.Furthermore,mutantthinfilamentshadreducedCaaffinitycomparedwithnormal.Conclusions:Th
6、efunctionalalterationsmirrorcloselyaconsistentphenotypefoundinprovenDCMmutationsinotherthinfilamentproteins,thussupportingtheinterpretationthatthesemutationsaredisease-causing.ThesearethefirstreportedautosomaldominantDCM-causingmutationsinTNNI3,andsothefindingsexpandthespectrumofdise
7、ase-causinggenesthatleadtoeitherhypertrophiccardiomyopathyorDCMdependingontheDownloadedfromhttp://ahajournals.orgbyonAugust12,2018specificmutation.(CircRes.2009;105:375-382.)2KeyWords:Caregulationcardiomyopathycontractilitydilatedcardiomyopathymutationilatedcardiomyopathy(DCM)ha
8、saprevalence
