两个遗传性凝血因子Ⅺ(F Ⅺ)缺陷症家系F Ⅺ基因突变分析

F Ⅺ gene mutations in two pedigrees of congenital clotting factor Ⅺ deficiency

目的 检测两个中国汉族人遗传性凝血因子Ⅺ缺陷症家系中FⅪ基因的突变。方法 检测先证者及家系成员血浆FⅪ∶C及FⅪ∶Ag ,并以其外周血单个核细胞中提取的基因组DNA为模板 ,PCR扩增FⅪ基因的所有外显子及其侧翼内含子序列 ,用DNA测序仪检测FⅪ的基因突变。结果 在两个家系中共发现三种基因突变 ,Trp2 2 8stop、Glu32 3Lys和Leu172Pro ,均为杂合型 ,且Leu172Pro为两个家系所共有。结论 三种FⅪ基因突变Trp2 2 8stop、Glu32 3Lys和Leu172Pro是导致中国人遗传性FⅪ缺陷的分子发病机制之一 ,突变Leu172Pro为国际首次发现。

Objectives To identify the FⅪ gene mutations in two Chinese pedigrees of congenital factor Ⅺ deficiency. Methods The peripheral blood samples were collected from the probands and their family members and the plasma FⅪ:C and FⅪ:Ag were determined. All the exons and exon-intron boundries of FⅪ gene were amplified with PCR and sequenced thereafter. Results A nonsense mutation Trp228stop and two missense mutations Glu323Lys and Leu172Pro were disclosed in the two pedigrees. All mutations existed in a heterozygous state. Conclusion The FⅪ gene mutations Trp228stop,Glu323Lys and Leu172Pro attribute to the pathogenesis of the congenital factor Ⅺ deficiency in Chinese. The Leu172Pro is identified for the first time.