Danon病临床研究进展

Danon*100037AdvancesinDanonDiseaseClinicalResearchCAIChiFANChao-meiKeyLaboratoryofClinicalTrialResearchinCardiovascularDrugsMinistryofHealthCardiovascularInstituteandFuwaiHospitalPekingUnionMedicalCollegeandChineseAcademyofMedicalSciencesBeijing100037China1004-3934201201-0039-04R542．2ADOI10．3969/j．issn．1004-3934．2012．01．012DanonX、。ⅡⅡDanon。Danon。DanonⅡAbstractDanondiseaseanX-linkedlysosomediseasecausedbythemutationsofgenesencodinglysosome-associatedmembraneprotein-2whichisahighlyglycosylatedproteinandanimportantconstituentofthelysosomalmembraneischaracterizedclinicallybythetri-adofcardiomyopathymyopathyandmentalretardation．Danondiseaseproducesacardiomyopathythatclinicallymimicshypertrophiccar-diomyopathyduetosarcomereproteinmutations．ThisarticlereviewsthepathogenesisandclinicalprofileofDanondisease．KeywordsDanondiseaselysosome-associatedmembraneprotein-2pathogenesisclinicalprofile1981Danon12hypertrophiccardiomyopathyHCM“”DanonDanondisease。Danon、。DanonX2-320。Ⅱlysosome-associatedmembraneprotein-2LAMP2Danon4-520LAMP26-7LAMP2Danon。12000Nishino4LAMP2Danon。Charron5197HCMLAMP24657CT1prematuretransla-tional-terminationcodonPTC1173_179del71。DanonHCM1%2/1973%2/73DanonHCM2/4HCMLAMP2。Yang750115HCM2LAMP21075C→T467T→G。HCMLAMP24%2/50LAMP2DanonHCM。1985Lewis8LAMP2LAMP2ⅠNC4。LAMP2C·93·20121331AdvCardiovascDisJanuary2012Vol．33No．1*“”－《》[e-mail]11LAMP2。N16～20N。LAMP240～45kDa≈4．0×104～4．5×104LAMP2120kDa≈12．0×104。LAMP2Xq24-q2591233410。LAMP291～89N9C。LAMP23LAMP2A、LAMP2BLAMP2C10LAMP2LAMP2ALAMP2C、LAMP2B。LAMP2Danon1．1LAMP2Danon、、、、。LAMP211。。46kDa≈4．6×1046。1．2LAMP2LAMP2ALAMP9chaperone-mediatedautophagyCMACMAMHCⅡ。Kovacs12lamp2y/-lamp1-/-lamp2y/-CMA。。LAMP1LAMP2LAMP2LAMP150%LAMPsLAMP1LAMP2GTP。LAMP2LAMP1。LAMP2LAMP113LAMPsLAMP2。1．3LAMP2LAMP1LAMP2。LAMP2。2DanonHCM。。LAMP2。。LAMP2。。C5b9C5b914。3Danon、。HCMDanonDanon。Yang7·04·20121331AdvCardiovascDisJanuary2012Vol．33No．1DanonLAMP2。LAMP2DanonArad6Maron2HCMDanon、、。、。15。Danon。、、。HCMT、Ⅲ、、Q14。4Danon。HCM、、。HCMDanonHCMDanon。LAMP2DanonLAMP2。Danon⑴。LAMP2⑵XX-linkedmyopathywithexcessiveautophagyXMEAXq24VMA21C5b-9DanonDanonXMEALAMP1LAMP2⑶PompPASα-、1～2。5Danon。HCMβ。DanonMaron7ICD4ICDICDDanon。Danon1416。HCMDanon。20201930。HCM1%～2%10%17。Danon。6DanonXLAMP2。DanonHCMmetabolichypertrophiccardiomyop-athymetabolicHCM18HCMDanon。DanonDanon。1DanonMJOhSJDimauroSetal．LysosomalglycogenstoragediseasewithnormalacidmaltaseJ．Neurology198131151-57．2MaronBJRobertsWCAradMetal．Clinicaloutcomeandphenotypicex-pressioninLAMP2cardiomyopathyJ．JAMA2009301121253-1259．3SabourdyFMichelakakisHAnastasakisAetal．DanondiseasefurtherclinicalandmolecularheterogeneityJ．MuscleNerve2009396837-844．4NishinoIFuJTanjiKetal．PrimaryLAMP-2deficiencycausesX-linkedvacuolarcardiomyopathyandmyopathyDanondiseaseJ．Nature20004066798906-910．5CharronPVillardESébillonPetal．Danon’sdiseaseasacauseofhyper-trophiccardiomyopathyasystematicsurveyJ．Heart2004908842-846．6AradMMaronBJGorhamJMetal．GlycogenstoragediseasespresentingashypertrophiccardiomyopathyJ．NEnglJMed20053524362-372．·14·20121331AdvCardiovascDisJanuary2012Vol．33No．17YangZMcmahonCJSmithLRetal．DanondiseaseasanunderrecognizedcauseofhypertrophiccardiomyopathyinchildrenJ．Circulation2005112111612-1617．8LewisVGreenSAMarshMetal．GlycoproteinsofthelysosomalmembraneJ．JCellBiol198510061839-1847．9Marie-GenevieveMJeanneMChenJWetal．Twohumanlysosomalmem-braneglycoproteinsh-lamp-1andh-lamp-2areencodedbygeneslocalizedtochromosome13q34andchromosomeXq24-25respectivelyJ．JBiolChem1990265137548-7551．10EskelinenELCuervoAMTaylorMRetal．UnifyingnomenclaturefortheisoformsofthelysosomalmembraneproteinLAMP-2J．Traffic20056111058-1061．11TanakaYGuhdeGSuterAetal．AccumulationofautophagicvacuolesandcardiomyopathyinLAMP-2-deficientmiceJ．Nature20004066798902-906．12KovacsWJShackelfordJETapeKNetal．Disturbedcholesterolhomeosta-sisinaperoxisome-deficientPEX2knockoutmousemodelJ．MolCellBiol20042411-13．13BeertsenWWillenborgMEvertsVetal．Impairedphagosomalmaturationinneutrophilsleadstoperiodontitisinlysosomal-associatedmembraneprotein-2knockoutmiceJ．JImmunol20081801475-482．14SugieKYamamotoAMurayamaKetal．Clinicopathologicalfeaturesofge-neticallyconfirmedDanondiseaseJ．Neurology200258121773-1778．15LaforêtPCharronPMaisonobeTetal．Charcot-Marie-ToothfeaturesandmaculopathyinapatientwithDanondiseaseJ．Neurology20046381535．16Echaniz-LagunaAMohrMEpaillyEetal．NovelLamp-2genemutationandsuccessfultreatmentwithhearttransplantationinalargefamilywithDanondiseaseJ．MuscleNerve2006333393-397．17MaronBJ．HypertrophiccardiomyopathyasystematicreviewJ．JAMA2002287101308-1320．18ColanSDLipshultzSELoweAMetal．Epidemiologyandcause-specificoutcomeofhypertrophiccardiomyopathyinchildrenfindingsfromthePediat-ricCardiomyopathyRegistryJ．Circulation20071156773-781．2011-07-25PRKAG2200433AdvancesinResearchonPathogenesisofPRKAG2CardiacSyndromeYEZhongZHANGBi-liZHENGXingDepartmentofCardiologyChanghaiHospitalofTheSecondMilitaryMedicalUniversityShanghai200433China1004-3934201201-0042-04R541．7R542．2ADOI10．3969/j．issn．1004-3934．2012．01．013PRKAG2γ2PRKAG2、。PRKAG2、PRKAG2。PRKAG2。PRKA