摘要目的 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.

abstractsObjective 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.