【摘要】 为了从分子水平阐明血小板无力症的发病机理，对一例Ⅰ型血小板无力症进行了系列研究。用抗血小板膜糖蛋白Ⅱｂ，Ⅲａ（ＧＰⅡｂⅢａ）单克隆抗体（ＳＺ－２２，２１）作免疫印迹分析发现患者ＧＰⅡｂ，Ⅲａ明显减少；完整血小板膜表面Ⅱｂ，Ⅲａ和αｖβ３结合试验显示患者几乎缺乏ＧＰⅡｂ，Ⅲａ复合物，而αｖβ３复合物数量增加，提示原发缺陷位于ＧＰⅡｂ；提取患者ＤＮＡ对ＧＰⅡｂ全部３０个外显子和启动子序列进行ＰＣＲ－单链构象多态性－测序研究发现，患者ＧＰⅡｂ第１３外显子第８６５８～８６７３位核苷酸１６个碱基缺失，对应于ＧＰⅡｂ第３、４钙离子结合之间第４００～４０５位６个氨基酸丢失（精４００－丝－精－脯－丝－谷氨酰－４０５），该缺陷可能改变了ＧＰⅡｂ钙离子结合的结构和空间构象，使ＧＰⅡｂ，Ⅲａ复合物不能形成，或虽有复合物形成但不稳定而容易被降解。更多还原

【Abstract】 WiththepurposeofstudyingthemolecularpathogenesisofGlanzmannthrombasthenia(GT),aninheritedbleedingdiseasecausedbydefectiveplateletmembraneglycoproteinⅡb,Ⅲa(GPⅡbⅢa),weinvestigatedaType-ⅠGTpatient.ImmunoblotassaywithmonoclonalantibodySZ-21(toGPⅢa)andSZ-22(toGPⅡb)showedthepatient’smarkeddeficiencyofGPⅡbⅢa;theGPⅡbⅢaandαvβ3bindingstudyofintactplateletsrevealedthatthepatienthadalmostnoGPⅡb,Ⅲacomplexexpressedonherplatelets,butαvβ3wasincreased,indicatingadefectmightbeinGPⅡb.Thepatient’sDNAwaspreparedandalexonsand5′-UTpromotorsregionofGPⅡbwasanalysedbyPCR-SSCPandsequencing.Theresultshowedtherewas16bp(8658-8673)deletioninexon13ofGPⅡb,corespondingto6aminoacids(400-RSRPSQ-405)deletionbetweenthethirdandfourthcalciumbind-ingdomainsontheheavychainofGPⅡb.ThisdefectprobablychangedthestructureandconformationofcalciumbindingdomainsonGPⅡb,whichmighthandicaptheformationofGPⅡb,Ⅲacomplex,oralthoughtherewasGPⅡb,Ⅲaformationonplateletmembranesurface,thecomplexwasunstableandwaseasilydegraded.更多还原