摘要
目的 探讨两个遗传性凝血因子Ⅶ (FⅦ )缺乏症家系的基因突变类型。方法 用DNA直接测序法对 2例患者及其家庭成员FⅦ基因进行分析 ;应用等位基因特异PCR(ASPCR)以及PCR辅助酶切反应鉴定是否有基因改变。结果 家系A中先证者有两种基因突变 :6 390位T→G导致Trp40Cys,11496位G→A导致Arg35 3Gln ,这两个突变均为杂合子 ;PCR辅助MspⅠ酶切证实其母亲也是杂合子Arg35 3Gln。家系B的先证者有 11482T→G ,导致His34 8Gln ,PCR辅助NspⅠ酶切证实先证者及其女含有同样的杂合子基因突变 ;还发现有 115 14位C→T导致Thr35 9Met,ASPCR证实先证者及其子携带同样的杂合子突变基因。结论 在两个遗传性FⅦ缺乏症家系中找到 3种FⅦ基因的错义突变 ,其中Trp40Cys为首次报道。
Objective To identify the mutation of coagulation factor Ⅶ(FⅦ) gene in two pedigrees with hereditary FⅦ deficiency. Methods FⅦ gene mutations were analysed in two propositi and their family members by direct DNA sequencing. Allele specific PCR and PCR combined with restricted enzyme digestion were used to confirm the detected mutations. Results Two gene mutations were detected in the propositus of pedigree A: G to C transition at position 6390 resulting in Trp40Cys and G to A at 11496 resulting in Arg353Gln, both are heterozygotes. The heterozygosity for polymorphism Arg353Gln was confirmed with the restriction enzyme MspⅠ digestion in his mother. In the propositus of pedigree B, there was a T to G transition at position 11482 resulting in His348Gln, heterozygosity of which was confirmed with NspⅠ digestion in the propositus and his daughter. G to T transition at position 11514 resulting in Thr359Met was also found in the propositus of pedigree B, and the heterozygosity for Thr359Met was confirmed with allele specific PCR in the propositus and his son. Conclusion Three missense mutations were found in two pedigrees with hereditary FⅦ deficiency. A novel Trp40Cys mutation was reported for the first time.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2002年第3期130-133,共4页
Chinese Journal of Hematology
