中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2011年
12期
854-857
,共4页
王明山%金艳慧%郑芳秀%谢海啸%徐鹏飞%牛真珍
王明山%金豔慧%鄭芳秀%謝海嘯%徐鵬飛%牛真珍
왕명산%금염혜%정방수%사해소%서붕비%우진진
因子Ⅶ缺乏%因子X缺乏%突变%血液凝固障碍%聚合酶链反应
因子Ⅶ缺乏%因子X缺乏%突變%血液凝固障礙%聚閤酶鏈反應
인자Ⅶ결핍%인자X결핍%돌변%혈액응고장애%취합매련반응
FⅦ deficiency%FX deficiency%Mutation%Blood coagulation disorder%Polymerase chain reaction
目的 对1例遗传性凝血因子Ⅶ(FⅦ)与因子X(FX)联合缺陷患者进行基因分析和家系调查,鉴定导致FⅦ与FX联合缺陷症的基因突变.方法 检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原、FⅦ促凝活性(FⅦ:C)、FX:C及FⅦ抗原(FⅦ:Ag)、FX:Ag等进行表型诊断；用DNA直接测序法分析先证者FⅦ、FX基因的全部外显子、侧翼、5’和3’非翻译区及家系成员相应的突变位点区域；选择106名健康体检者作对照.结果 先证者PT、APTT延长,分别为84.5 s和63.4 s,FⅦ:C、FⅦ:Ag和FX:C、FX:Ag分别为6％、7％和4％、30％；先证者父亲、母亲、姐姐的PT稍延长,FⅦ:C分别为72％、47％、42％,FX:C分别为76％、54％、47％,FX:Ag分别为100％、69％、58％,其APTT、FⅦ:Ag均无明显异常.先证者FⅦ基因外显子8的g.11267C→T纯合突变导致Arg277Cys,FX基因外显子8的g.28139G→T纯合突变导致Val384Phe；其父亲、母亲、姐姐均存在FⅦ基因g.11267C→T和FX基因g.28139G→T杂合子.结论 FⅦ和FX基因分别存在的Arg277Cys、VM384Phe纯合突变是导致先证者FⅦ与FX联合缺陷的分子机制；Val384Phe突变为国际首次报道,推测可能影响FX蛋白合成或分泌功能.
目的 對1例遺傳性凝血因子Ⅶ(FⅦ)與因子X(FX)聯閤缺陷患者進行基因分析和傢繫調查,鑒定導緻FⅦ與FX聯閤缺陷癥的基因突變.方法 檢測凝血酶原時間(PT)、活化部分凝血活酶時間(APTT)、纖維蛋白原、FⅦ促凝活性(FⅦ:C)、FX:C及FⅦ抗原(FⅦ:Ag)、FX:Ag等進行錶型診斷；用DNA直接測序法分析先證者FⅦ、FX基因的全部外顯子、側翼、5’和3’非翻譯區及傢繫成員相應的突變位點區域；選擇106名健康體檢者作對照.結果 先證者PT、APTT延長,分彆為84.5 s和63.4 s,FⅦ:C、FⅦ:Ag和FX:C、FX:Ag分彆為6％、7％和4％、30％；先證者父親、母親、姐姐的PT稍延長,FⅦ:C分彆為72％、47％、42％,FX:C分彆為76％、54％、47％,FX:Ag分彆為100％、69％、58％,其APTT、FⅦ:Ag均無明顯異常.先證者FⅦ基因外顯子8的g.11267C→T純閤突變導緻Arg277Cys,FX基因外顯子8的g.28139G→T純閤突變導緻Val384Phe；其父親、母親、姐姐均存在FⅦ基因g.11267C→T和FX基因g.28139G→T雜閤子.結論 FⅦ和FX基因分彆存在的Arg277Cys、VM384Phe純閤突變是導緻先證者FⅦ與FX聯閤缺陷的分子機製；Val384Phe突變為國際首次報道,推測可能影響FX蛋白閤成或分泌功能.
목적 대1례유전성응혈인자Ⅶ(FⅦ)여인자X(FX)연합결함환자진행기인분석화가계조사,감정도치FⅦ여FX연합결함증적기인돌변.방법 검측응혈매원시간(PT)、활화부분응혈활매시간(APTT)、섬유단백원、FⅦ촉응활성(FⅦ:C)、FX:C급FⅦ항원(FⅦ:Ag)、FX:Ag등진행표형진단；용DNA직접측서법분석선증자FⅦ、FX기인적전부외현자、측익、5’화3’비번역구급가계성원상응적돌변위점구역；선택106명건강체검자작대조.결과 선증자PT、APTT연장,분별위84.5 s화63.4 s,FⅦ:C、FⅦ:Ag화FX:C、FX:Ag분별위6％、7％화4％、30％；선증자부친、모친、저저적PT초연장,FⅦ:C분별위72％、47％、42％,FX:C분별위76％、54％、47％,FX:Ag분별위100％、69％、58％,기APTT、FⅦ:Ag균무명현이상.선증자FⅦ기인외현자8적g.11267C→T순합돌변도치Arg277Cys,FX기인외현자8적g.28139G→T순합돌변도치Val384Phe；기부친、모친、저저균존재FⅦ기인g.11267C→T화FX기인g.28139G→T잡합자.결론 FⅦ화FX기인분별존재적Arg277Cys、VM384Phe순합돌변시도치선증자FⅦ여FX연합결함적분자궤제；Val384Phe돌변위국제수차보도,추측가능영향FX단백합성혹분비공능.
Objective To perform gene analysis and family survey of a patient with combined inherited F Ⅶ and F X deficiency,and to identify the gene mutation of this patient.Methods The phenotype diagnosis was validated by coagulant parameter assay on prothrombin time ( PT),activated partial thromboplastin time (APTT),fibrinogen,FⅦ and FX activity (FⅦ:C,FX:C) and FⅦ and FX antigen (FⅦ:Ag,FX:Ag).FⅦ and FX gene mutations were analyzed in the proband and other family members by DNA direct sequencing of all exons,exon-intron boundaries and 5',3' untranslated sequences.One hundred and six health examination participants were selected as control.Results The values of PT and APTT of the proband showed significantly prolonged,which were 84.5s and 63.4s,respectively.The levels of FⅦ:C,FⅦ:Ag,FX:C and FX:Ag were 6％,7％,4％ and 30％,respectively.The PT of his father,mother and sister was prolonged slightly while both APTT and FⅦ:Ag were in the normal range.Two homozygous mutations,g.11267C→T in exon 8 of FⅦ gene resulting in the substitution of Arg277Cys and g.28139G→T in exon 8 of F X gene leading to the substitution of Val384Phe,were identified in the proband.The proband' s parents and sister were heterozygous for Arg277Cys and Val384Phe mutations.Conclusion Homozygous mutation Arg277Cys in FⅦ gene and Val384Phe in FX gene were the molecular mechanism causing combined inherited FⅦ and FX deficiency.The Val384Phe substitution was a novel mutation,which may affect the synthesis or secretion of F X protein.
