Glu29→Gly纯合子突变导致的遗传性凝血酶原缺乏症

Prothrombin deficiency resulted from a homozygous Glu29 to Gly mutation in the prothrombin gene

目的 对 1个遗传性凝血酶原缺乏症家系进行凝血酶原 (FⅡ )基因突变的检测。方法 用活化的部分凝血活酶时间 (APTT) ,凝血酶原时间 (PT)及FⅡ促凝活性 (FⅡ∶C)、FⅡ抗原 (FⅡ∶Ag)测定进行表型诊断 ;用PCR法对先证者的FⅡ基因 14个外显子及其侧翼序列和 5′端非翻译区 (5′UTR)、3′端非翻译区 (3′UTR)序列进行扩增 ,PCR产物纯化后直接测序 ,检测其基因突变。家系成员DNA在先证者FⅡ基因突变区域扩增后测序。突变位点经限制性内切酶分析证实。 10 3名健康献血者作对照。结果 先证者表型诊断为凝血酶原缺乏症 (Ⅰ型 ) ;FⅡ外显子区共发现 3个与文献报道的FⅡ基因序列不同的位点 ,其中位于第 2外显子区的为纯合突变A6 0 1G。家系分析表明先证者父亲、母亲和外祖母均为A6 0 1G杂合子。结论 纯合错义突变A6 0 1G引起的Glu2 9→Gly是导致该例遗传性凝血酶原缺乏的原因。

Objective To investigate the gene mutations in a pedigree with inherited prothrombin (FⅡ) deficiency. Methods The activated partial thromboplastin time (APTT),prothrombin time (PT), FⅡ activity ( FⅡ ∶C) and FⅡ antigen(FⅡ∶Ag) test were used for phenotype diagnosis. The genomic DNA was extracted from the peripheral blood of the propositus. All the 14 exons , intron/exon boundaries and the 5′and 3′ untranslated regions (UTR) of the prothrombin gene were amplified by polymerase chain reaction (PCR). The PCR products were screened by direct sequencing and the mutations detected were further confirmed by restricted enzyme digestion. One hundred and three healthy blood donors were used as controls. Results The phenotype of the propositus was prothrombin deficiency(type Ⅰ). With reference to the prothrombin nucleotide sequence published by Degen & Dacie, three variations were found in the FⅡ gene of the propositus. Among them, the novel mutation was a homozygous A601G subtitution in exon 2. Conclusion The prothrombin deficiency of the propositus is caused by a homozygous Glu29 to Gly mutation in the prothrombin gene.