1例家族性凝血因子Ⅺ缺乏症基因突变及家系调查

Survey and analysis for genetic mutation in a pedigree of congenital coagulation factor Ⅺ deficiency

目的分析1例凝血因子Ⅺ(FⅪ)缺乏症家系的基因缺陷。方法检测先证者及其家系成员的活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)及FⅪ活性,PCR扩增家系成员中FⅪ基因,通过直接测序法分析FXI基因突变。结果患儿家系中7位成员APTT显著延长,FⅪ活性明显下降。先证者及多个家系成员中发现FⅪ基因第8号外显子有一c.841C>T(p.Gln263stop)无义突变。还发现3个多态性位点,分别是第8呈外显子c.801A>G(p.Thr249Thr)同义突变,第15号外显子c.1812G>T(p.Arg586Arg)及c.1839G>A(p.Glu595Glu)同义突变。结论 c.841C>T(p.Gln263stop)杂合突变是导致此家系FⅪ缺乏的基因发病机制。

Objective To analyze the gene defect of a Chinese pedigree diagnosed with congenital coagulation Factor Ⅺ deficiency.Methods Activated partial thromboplastin time( APTT),prothrombin time( PT) and FⅪ activity( FⅪ: C) were assayed in the proband and other numbers of the family. PCR amplification and direct sequencing were used to investigate the mutation of FⅪ gene.Results Seven members of the family showed prolonged APTT and reduced FⅪ: C activity. Seven members of this family,a nonsense mutation,c.841 C>T( p.Gln263 stop) in exon 8 of FⅪ gene was found in all of the seven members. Three synonymous mutations were found,i.e.,c.801 A>G( p.Thr249 Thr) in exon 8,c.1812 G>T( p.Arg586 Arg) and c.1839 G>A( p.Glu595 Glu) in exon 15. Conclusion c.841 C>T( p.Gln263 stop) heterozygous mutation should be the genetic pathogenesis for the congenital FⅪ deficiency in this pedigree.