家族性肥大性心肌病致病基因定位及突變篩查.pdf

1、中國協(xié)和醫(yī)科大學中國醫(yī)學科學院碩士學位論文家族性肥大性心肌病致病基因定位及突變篩查姓名：夏學傳申請學位級別：碩士專業(yè)：分子生物學指導教師：沈巖2002.5.1中國協(xié)和醫(yī)科大學碩士學位論文4ABSTRACTFamilialhypertrophiccardiomyopathy(FHC)isanautosomaldominantinheriteddieaseandischaracterisedbyunexplainedhypertrophyo

2、ftheheartmuscle，whichisoneofthemajorcauseofsuddendeathinyoungadultsTypicalpathologicalmanifestationofFHCincludesmyocytehypertrophydisarrayandinterstitialfibrosisClinicallyFHChasadiversecondition，rangesfromallasymptomatic

3、coursetoincidentsofdizzinessandsyncopes，chestpain，andsymptomsofheartfailureFHCisageneticallyheterogeneousdisordereitherinthephenotypeorinthegenotypeItcallbecausedbygenesindifferentchromosomesorbydifferentmutationsinonege

4、neMoleculargeneticanalysiseshaverevealedthatFHCisadiseaseofthecardiacsarcomereSo協(xié)，multiplemutationsinninedifferentgenesencodingscacomereproteinshavebeenidentifiedTheseareBmyosinheavychaingene(MYH7)in14q112q13，ventricular

5、myosinessentiallightchaingene(MYL3)in3p212213，ventricularmyosinregulatorylightchaingene(MYL2)in12q23—243，cardiacmyosinbindingproteinCgene(MYBPC3)in1lpl12，cardiacuactingene(ACTC)in15q，cardiactroponinTgene(TNNT2)inlq32，atr

6、opomyosingene(TPMI)in15q221，cardiactroponinIgene(TNNl3)in19q134q134，Titingene(T1N)in2q241Furthermore，aregionin7q3hasbeendectectedtobecosegregationwithFHCWeappliedgeneticlinkageanalysisinaChinesepedegreefromQindao，inwhich

7、threegenerationsincludingfortypeoplewereanalysizedatnineknowndiseasegenesandonereportedlocusTheresultsoftwopointLODanalysisshowsthatattheMYL3，MYL2，TNNT2，TNND，TPMl，MYBPC3，ACTC，”Ngeneandthe7q3loci，nolinkageisfoundbetweenth

8、egeneticmarkersandthediseasegenesinthepedegreeOnlyatthe2BmarkerinMYH7gene(14q112q13)canweseeapositiveLeDscoreO08when0=005DirectDNAsequencingwasperformedinthecandicategenesinthesuspiciousregionNovalueablemutationisfound，h