凝血因子Ⅻ缺陷症导致再发体外受精和胚胎移植失败原因2例分析

Factor Ⅻ deficiency in two women with recurrent in vitro fertilization-embryo transfer failure

目的 :探讨机体凝血因子Ⅻ(FⅫ)水平对再发体外受精和胚胎移植(IVF-ET)的影响。方法:检测患者凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血因子Ⅻ促凝活性(FⅫ:C)、纤溶酶原活性(PLG:C)、D-二聚体(D-D)等凝血指标;PCR扩增FⅫ基因的14个外显子及其侧翼序列,进行DNA测序,发现基因突变,则反向测序予以证实。50例正常对照组用于排除FⅫ基因多态性。结果:2例FⅫ缺陷患者APTT显著延长,FⅫ:C明显降低。患者1基因分析发现g.6753delACA杂合突变(国内外鲜见报道)和46T/T。患者2发现g.7142insertC杂合突变和46C/T。结论:FⅫ缺陷症患者易导致机体纤溶功能下降,是引起患者IVF-ET失败的重要原因之一。

Objective： To identify the possible correlation of FⅫ deficiency with recurrent IVF-ET failure Methods： Prothrombin time （PT）, activated partial thromboplastin time （APTT）, FⅫ procoagulant activity （FⅫ：C）, Plasminogen activity, D-Dimer and other coagulant parameters were detected. Exons 1-14, boundary introns including the splice junctions of the FⅫ gene were amplified with Polymerase chain reaction （PCR）. The PCR products were purified and sequenced directly. If a gene mutation was found, then reverse sequence to confirm it. Fifty heathy persons as normal controls. Results： Both APTT in the two patients were significantly prolonged. And the FⅫ：C values of the patients were low. Patient 1 was found heterozygous deletion mutation g.6753delACA in exon 9 and 46T/T genetype in the promoter region of FXU gene. Patient 2 was found heterozy- gous insert mutation g.7142 insertC in exon 10 and 46C/T genetype. The mutation of FⅫ g.6753delACA was a new mutation. Conclusion： FXII deficiency may contribute to impairment of fibrinolytic activity. Decreased FXII activity may be one of the important reasons of recurrent IVF-ET failure.