摘要目的：对两个家系中重型 A 型血友病(hemophilia A,HA)患者的凝血因子Ⅷ基因(factorⅧ,F8)进行倒位检测,为家系提供遗传咨询和产前诊断。方法收集家系先证者外周血、胎儿羊水和绒毛细胞,应用反向转变 PCR(inverse-shifting PCR,IS-PCR)检测第1内含子倒位(intron 1 inversion,Inv1)或第22内含子倒位(intron 22 inversion,Inv22),并明确 Inv-22的亚型。结果IS-PCR 检测结果显示家系1先证者为 Inv22倒位者,先证者母亲为 Inv22倒位携带者,其他家系成员未检测到 Inv22倒位；Inv1检测结果显示均无 Inv1倒位。家系2先证者为 Inv1倒位者,先证者姐姐为 Inv1倒位携带者,另3名家系成员未检测到 Inv1倒位；Inv22检测结果显示,均无 Inv22。结论通过 IS-PCR 检测出两个家系中 Inv22或 Inv1的患者和携带者,并能明确 Inv22的亚型,为家系的遗传咨询和产前诊断提供了依据。

abstractsObjective Inversions of intron 1 (Inv1)or intron 22 (Inv22)of the coagulation factor Ⅷgene (F8)may be found in 40%-50% of patients with severe hemophilia A.Such inversions cannot be detected by conventional sequencing.Due to homologous recombination,family-based linkage analysis may yield false positive or false negative results.In this study,Inverse-shifting PCR (IS-PCR)was used to detect potential inversions in two families affected with hemophilia A.Methods Peripheral venous blood, fetal amniotic fluid and fetal chorionic cells were harvested for genome DNA extraction.IS-PCR was used to detect Inv1 or Inv22 detection or its subtypes.Results IS-PCR has accurately detected Inv22 and Inv1 in both families and verified the subtypes of Inv22.Conclusion Carriers of Inv22 or Inv1 may be precisely detected with IS-PCR.The results have provided valuable information for genetic counseling and prenatal diagnosis for the affected families.