中华内科杂志
中華內科雜誌
중화내과잡지
CHINESE JOURNAL OF INTERNAL MEDICINE
2012年
10期
788-792
,共5页
姜林林%曹雅楠%王学锋%丁秋兰%许冠群%张利伟%戴菁%陆晔玲%王鸿利%奚晓东
薑林林%曹雅楠%王學鋒%丁鞦蘭%許冠群%張利偉%戴菁%陸曄玲%王鴻利%奚曉東
강림림%조아남%왕학봉%정추란%허관군%장리위%대정%륙엽령%왕홍리%해효동
von Willebrand病%von Willebrand因子%突变
von Willebrand病%von Willebrand因子%突變
von Willebrand병%von Willebrand인자%돌변
von Willebrand disease%von Willebrand factor%Mutation
目的 分析3例遗传性血管性血友病(vWD)患者的表型和基因型,探讨其分子发病机制.方法 采用出血时间(BT)、APTT、瑞斯托霉素诱导的血小板聚集试验(RIPA)、血管性血友病因子(vWF)瑞斯托霉素辅因子活性(vWF∶Rco)、vWF抗原(vWF∶Ag)、vWF活性(vWF∶A)、vWF胶原结合试验(vWF∶CB)和多聚体分析对3例vWD患者进行表型诊断,通过血栓弹力图检测分析全血凝固功能.提取外周血基因组DNA,测序分析vWF基因突变情况.结果 3例先证者APTT、BT均延长,vWF∶Rco 、vWF∶ Ag、vWF∶A和vWF∶ CB均不同程度减低,除先证者A外,先证者B、C血浆RIPA明显减低,多聚体分析结果显示先证者A和C血浆多聚体分布基本正常,先证者B大相对分子质量多聚体缺失.先证者C血栓弹力图检测全血呈明显低凝状态.基因测序发现,先证者A、B和C分别存在26号外显子g.106782G＞T(Cys1130Phe)、28号外显子g.110988G＞A(Gly1579Arg)和28号外显子g.110373C＞T(Arg1374Cys)的杂合错义突变.结论 3例先证者表型诊断分别为1型、2A型和2M型vWD,Cys1130Phe、Gly1579Arg和Arg1374Cys的杂合错义突变分别为3例先证者的致病基础.
目的 分析3例遺傳性血管性血友病(vWD)患者的錶型和基因型,探討其分子髮病機製.方法 採用齣血時間(BT)、APTT、瑞斯託黴素誘導的血小闆聚集試驗(RIPA)、血管性血友病因子(vWF)瑞斯託黴素輔因子活性(vWF∶Rco)、vWF抗原(vWF∶Ag)、vWF活性(vWF∶A)、vWF膠原結閤試驗(vWF∶CB)和多聚體分析對3例vWD患者進行錶型診斷,通過血栓彈力圖檢測分析全血凝固功能.提取外週血基因組DNA,測序分析vWF基因突變情況.結果 3例先證者APTT、BT均延長,vWF∶Rco 、vWF∶ Ag、vWF∶A和vWF∶ CB均不同程度減低,除先證者A外,先證者B、C血漿RIPA明顯減低,多聚體分析結果顯示先證者A和C血漿多聚體分佈基本正常,先證者B大相對分子質量多聚體缺失.先證者C血栓彈力圖檢測全血呈明顯低凝狀態.基因測序髮現,先證者A、B和C分彆存在26號外顯子g.106782G＞T(Cys1130Phe)、28號外顯子g.110988G＞A(Gly1579Arg)和28號外顯子g.110373C＞T(Arg1374Cys)的雜閤錯義突變.結論 3例先證者錶型診斷分彆為1型、2A型和2M型vWD,Cys1130Phe、Gly1579Arg和Arg1374Cys的雜閤錯義突變分彆為3例先證者的緻病基礎.
목적 분석3례유전성혈관성혈우병(vWD)환자적표형화기인형,탐토기분자발병궤제.방법 채용출혈시간(BT)、APTT、서사탁매소유도적혈소판취집시험(RIPA)、혈관성혈우병인자(vWF)서사탁매소보인자활성(vWF∶Rco)、vWF항원(vWF∶Ag)、vWF활성(vWF∶A)、vWF효원결합시험(vWF∶CB)화다취체분석대3례vWD환자진행표형진단,통과혈전탄력도검측분석전혈응고공능.제취외주혈기인조DNA,측서분석vWF기인돌변정황.결과 3례선증자APTT、BT균연장,vWF∶Rco 、vWF∶ Ag、vWF∶A화vWF∶ CB균불동정도감저,제선증자A외,선증자B、C혈장RIPA명현감저,다취체분석결과현시선증자A화C혈장다취체분포기본정상,선증자B대상대분자질량다취체결실.선증자C혈전탄력도검측전혈정명현저응상태.기인측서발현,선증자A、B화C분별존재26호외현자g.106782G＞T(Cys1130Phe)、28호외현자g.110988G＞A(Gly1579Arg)화28호외현자g.110373C＞T(Arg1374Cys)적잡합착의돌변.결론 3례선증자표형진단분별위1형、2A형화2M형vWD,Cys1130Phe、Gly1579Arg화Arg1374Cys적잡합착의돌변분별위3례선증자적치병기출.
Objective To analyze the phenotype and genotype of three patients with yon Willebrand disease (vWD),and to explore its molecular pathogenesis.Methods Bleeding time (BT),APTT,ristocetin induced platelet aggregation (RIPA),von Willebrand factor (vWF):ristocetin cofactor (Rco)(vWF∶ Rco),vWF antigen (vWF∶ Ag),vWF activity (vWF∶ A) test,vWF collagen binding assay (vWF∶ CB) and multimer analysis were detected for phenotype diagnosis.The dynamic process of blood coagulation was evaluated by using the thrombelastography.Genomic DNA was extracted from the peripheral blood.The vWF gene mutation was detected by sequencing.Results APTT,BT were prolonged in the three probands.Plasma vWF∶ Rco,vWF∶ Ag,vWF∶ A and vWF∶ CB were decreased in different degrees.RIPA was reduced in probands B and C.vWF multimer analysis found the lost of the large molecular weight multimers in proband B,while basically normal in probands A and C.The dynamic process of blood coagulation of proband C presented obvious hypocoagulability by using the thrombelastography.Heterozygous missense mutation g.106782G ＞ T resulting in Cys1130Phe in exon 26,g.110988G ＞ A resulting in Gly1579Arg in exon 28 and g.110373C ＞T resulting in Arg1374Cys in exon 28 were found in the probands A,B and C,respectively.Conclusion Three probands were diagnosed as type 1,type 2A or type 2MvWD by phenotype detection.Heterozygous missense mutation Cys1130Phe,Gly1579Arg and Arg1374Cys induced vWD of three probands,respectively.
