一个遗传性凝血因子Ⅶ与X联合缺陷症家系的基因分析  

Gene analysis of a combined inherited factor Ⅶ and factor X deficiency pedigree

作　　者：王明山[1] 金艳慧[1] 郑芳秀[1] 谢海啸[1] 徐鹏飞[1] 牛真珍[1] 

机构地区：[1]温州医学院附属第一医院检验科,325000

出　　处：《中华血液学杂志》2011年第12期854-857,共4页Chinese Journal of Hematology

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。结果先证者胛、APTT延长，分别为84．5s和63．4s，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、Val384Phe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。Objective To perform gene analysis and family survey of a patient with combined inherited FⅦ 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 FVI] 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, F X： C and F X：Ag were 6% , 7% , 4% and 30% , respectively. The PT of his father, mother and sister was prolonged slightly while both APTT and F Ⅶ 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 Va1384Phe, were identified in the proband. The proband＇ s parents and sister were heterozygous for Arg277Cys and Va1384Phe mutations. Conclusion Homozygous mutation Arg277Cys in FVII gene and Va1384Phe in FX gene were the molecular mechanism causing combined inherited FVII and FX deficiency. The Va1384Phe substitution was a novel mutation, which may affect the synthesis or secretion of FX protein.

关 键 词：因子Ⅶ缺乏 因子X缺乏 突变 血液凝固障碍 聚合酶链反应 

分 类 号：R440[医药卫生—诊断学]