【摘 要】
：
背景 血友病A(Hemophilia A,HA)是最常见的X连锁隐性遗传性出血性疾病,其最主要病因是由于凝血因子Ⅷ(FⅧ)基因缺陷而导致FⅧ含量不足或活性下降,从而引起凝血功能障碍,多表现为自发性出血不止或手术、创伤后出血不止.临床上根据患者凝血因子Ⅷ促凝活性(FⅧ：C)将其分为重型、中性和轻型,比例分别为50％,10％,40％,其中重型HA中有约50％的是由于F8基因内含子22倒位突变引起的[1
【出 处】
：
中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议
论文部分内容阅读
背景 血友病A(Hemophilia A,HA)是最常见的X连锁隐性遗传性出血性疾病,其最主要病因是由于凝血因子Ⅷ(FⅧ)基因缺陷而导致FⅧ含量不足或活性下降,从而引起凝血功能障碍,多表现为自发性出血不止或手术、创伤后出血不止.临床上根据患者凝血因子Ⅷ促凝活性(FⅧ：C)将其分为重型、中性和轻型,比例分别为50％,10％,40％,其中重型HA中有约50％的是由于F8基因内含子22倒位突变引起的[1].由于内含子22倒位突变检测难度大,一直是限制HA基因诊断在临床上广泛开展的原因.本病尚无根治方法,只能以凝血因子Ⅷ相关制品替代治疗,因此,有必要开展HA的基因诊断及产前诊断,对携带者进行早期遗传学控制,防止此类患儿的出生.目的 对来我院就诊的13个HA家系先证者进行F8基因突变分析,并对家系中女性成员进行携带者检测及高危胎儿进行产前诊断.方法 应用IS-PCR(inverse shifting-polymerase chain reaction)对HA患者进行F8基因倒位检测,倒位检测阴性患者应用聚合酶链反应(PCR)和DNA测序的方法进行突变检测,仍未见突变的患者应用多重酶联依赖探针扩增(Multiplex ligation-dependent probe amplification,MLPA)进行重复突变检测.结果 IS-PCR检测出6例HA患者存在F8基因内含子22远端倒位突变；倒位检测阴性患者直接测序检出5例存在点突变,其中4例为未见报道的新突变,分别为：c.4875_4876insA,c.6267delG,c.994delT,IVS19-1G＞A；MLPA检测出1例患者存在exons 2～22重复突变,为未见报道的新突变；1例患者未见F8基因突变.携带者检测结果显示18例女性中10例为该病携带者；5个HA家系中高危胎儿产前诊断结果显示3例为女性携带者胎儿,1例为正常女性胎儿,1例为正常男性胎儿.结论 IS-PCR倒位检测结合直接测序及MLPA可有效的对HA患者及携带者进行基因诊断,并根据需要对家系中高危胎儿行产前诊断.
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