中文摘要：

目的检测重型血友病A（HA）患者凝血因子Ⅷ（FⅧ）基因内含子22倒位（INV22）的发生频率，探讨部分重型HA患者的发病机制，并对患者家系女性成员进行携带者诊断。方法126例重型HA患者均为男性，中位年龄14岁（4个月～63岁）。应用一期法检测凝血因子Ⅷ活性（FⅧ：C）；采用长距离PCR（LD—PCR）结合脉冲场凝胶电泳（PFGE）进行FⅧ基因1NV22检测，并对其中3例1NV22阳性患者进行家系调查。结果126例重型HA患者中检mINV22阳性患者52例（41．3％）。3个INV22阳性家系中疑为携带者的11例女性成员中检m携带者4例，其中3例为患者母亲，1例为患者胞姐。其中1个家系无家族史，该家系8名女性成员中除患者的姨表妹未检测外，其余7名成员检测结果显示患者母亲为INV22携带者，其外祖母及2个姨母、2个同胞姐妹及1个姨表姐均为非携带者。结论LD—PCR结合PFGE检测FⅧ基因INV22可用于部分重型HA患者和携带者基因诊断。

英文摘要：

Objective To investigate the incidence of intron 22 inversion （INV22） of factor Ⅷ （F Ⅷ ） gene in severe hemophilia A （HA） patients, clarify its pathological mechanism, and identify INV22 carrier in the female family members. Methods One-stage method was used to assay the F Ⅷ activity （FVnI ： C） in 126 severe HA patients with a median age of 14 years old （range： 4 months-63 years）. INV22 was analyzed by long-distance polymerase chain reaction （LD-PCR） and pulsed field gel electrophoresis （PFGE）, and pedigree were conducted in 3 involved HA families. Results Of all the 126 severe HA, 52 （41.3%） cases had the INV22. Four females including 3 mothers and 1 sister of probands were diagnosed as INV22 carriers among 11 suspected carrier mosaicisms from 3 INV22 positive HA families. In 8 females from one family without HA history, the patient＇ s mother was a INV22 carrier, but her maternal grandmother, 2 maternal aunts, 2 female siblings and 1 elder female cousin were negative. Conclusion LD-PCR and PFGE could be used to diagnose severe HA patients with 1NV22 and identify the carriers.