抗凝血酶基因杂合突变导致的抗凝血酶缺陷症

Antithrombin deficiency due to heterozygous antithrombin gene mutation and a pedigree study

目的对1例先天性抗凝血酶(AT)缺陷症患者及其家系成员进行 AT 表型及基因突变检测。方法采用发色底物法和免疫比浊法分别检测先证者及其家系成员血浆 AT 活性(AT:A)和AT 抗原含量(AT:Ag),并采用 PCR 法对先证者 AT 基因的7个外显子及其侧翼内含子序列进行扩增,PCR 产物纯化后直接测序检测基因突变。结果先证者的 AT:Ag 正常,但 AT:A 为正常值的65%,表现为Ⅱ型 AT 缺陷,其 AT 基因外显子6区第13830位核苷酸发生了 G→A杂合突变,引起Arg393His 错义突变。同样突变也见于该家系其他3名成员。结论该家系成员的Ⅱ型 AT 缺陷由AT 基因 G13830A 杂合突变所致,可致血栓形成。

Objective To identify the antithrombin （AT） phenotye and gene mutation of a kindred with hereditary antithrombin deficiency. Methods Plasma AT activity and AT antigen level of the propositus and his kindred members were determined with chromogenic substrate method and immunoassay, respectively. All the seven exons and intron-exon boundaries of antithrombin gene were analyzed by PCR and direct sequencing of amplified PCR products from the propositus. Results The propositus AT antigen level was normal but his AT activity was only 65% of normal value suggesting that he had type ⅡAT deficiency. A heterozygous G13830A mutation in exon 6 resulting in Arg393His missense mutation in his AT polypeptide was identified in the propositus. The same phenotype and gene mutation were found in other 3 kindred members. Conclusion The type ⅡAT deficiency found in this kindred is caused by heterozygous G13830A mutation in AT gene.