抗凝血酶基因杂合突变导致的抗凝血酶缺陷症

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。

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

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 II AT 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 II AT deficiency found in this kindred is caused by heterozygous G13830A mutation in AT gene.