血友病的携带者与产前分子诊断

Carrier detection and prenatal diagnosis on hemophilia

目的 建立一种简便、快速的血友病携带者检测与产前诊断体系。方法 用聚合酶链反应 (PCR)方法分别检测FⅧ内含子 2 2倒位及血友病A家系中FⅧ基因内的BclI位点、内含子 13和2 2中STR和FⅧ基因外的DXS 5 2 (ST14 )位点的多态性 ;对血友病B家系检测FⅨ基因外 6个STR位点(DXS1192、DXS12 11、DXS80 94、DXS80 13、DXS12 2 7、DXS10 2 )的多态性。结果 综合应用直接检测倒位和遗传连锁分析 ,2 1个血友病A家系的可诊断率为 94 7% ;联合FⅨ基因外 6个STR位点对血友病B家系进行遗传连锁分析 ,使 10个家系全部得到诊断。结论 FⅧ内含子 2 2倒位检测阳性 ,可以直接诊断血友病A的携带者及患儿 ;检测FⅧ基因内、外及FⅨ基因外多个位点的多态性并进行遗传连锁分析 ,是血友病携带者检测与产前诊断的简便、快速的方法。

Objective To establish a simple,rapid carrier detection and prenatal diagnosis system on hemophilia. Methods For hemophilia A family, factor Ⅷ intron 22 inversion and polymorphism of factor Ⅷ intragenic RFLP of Bcl I, STR within intron 13 and 22 ,as well as extragenic DXS 52(ST 14) VNTR were examined by polymerase chain reaction ;while hemophilia B family, the polymorphism of 6 extragenic loci of factor Ⅸ (DXS1192?DXS1211?DXS8094?DXS8013?DXS1227?DXS102)were detected. Results The comprehensive utilization of direct assay about factor Ⅷ intron 22 inversion and heredity linkage analysis, the total diagnostic rate of 21 hemophilia A families was 94.7%;all of 10 hemophilia B families were made final diagnosis by using 6 extragenic loci of factor Ⅸ respectively.Conclusions If the intron 22 inversion is present, we can determine the diagnosis of hemophilia A patients or carriers. It is a simpler and rapid method for the hemophilia carrier and prenatal diagnosis by detection of the intragenic and extragenic loci of factor Ⅷ and extragenic loci of factor Ⅸ and then heredity linkage analysis.