Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China,
Acta Haematol. 2020;143(3):260-265. doi: 10.1159/000502109. Epub 2019 Sep 3.
To study the molecular basis of hereditary antithrombin (AT) deficiency in a Chinese family. It will help us understand the pathogenesis of this type of disease.
AT activity (AT:A) and the AT antigen (AT:Ag) level were tested by chromogenic substrate and immunoturbidimetry, respectively. To identify the novel mutations, SERPINC1 gene sequencing was carried out. The possible impact of the mutations was analyzed by model and bioinformatic analyses.
AT:A and the AT:Ag level of the proband were 43% and 113 mg/L (normal range: 98-119% and 250-360 mg/L), respectively. Sequencing analysis revealed compound heterozygous mutations, including a frameshift mutation (c.318_319insT) resulting in Asn75stop and a missense mutation (c.922G>T) resulting in Gly276Cys. The bioinformatic and model analyses indicated that these mutations may disrupt the function and structure of the AT protein.
We detected 2 novel heterozygous mutations (c.318_319insT and c.922G>T) in the proband, and these were associated with decreased AT:A.
研究一个中国家族遗传性抗凝血酶（AT）缺陷的分子基础。这将有助于我们了解此类疾病的发病机制。
通过显色底物法和免疫比浊法分别检测 AT 活性（AT:A）和 AT 抗原（AT:Ag）水平。为了鉴定新的突变，我们进行了 SERPINC1 基因测序。通过模型和生物信息学分析，分析了突变的可能影响。
先证者的 AT:A 和 AT:Ag 水平分别为 43%和 113mg/L（正常范围：98-119%和 250-360mg/L）。测序分析显示存在复合杂合突变，包括导致 Asn75stop 的框移突变（c.318_319insT）和导致 Gly276Cys 的错义突变（c.922G>T）。生物信息学和模型分析表明，这些突变可能破坏 AT 蛋白的功能和结构。
我们在先证者中检测到 2 个新的杂合突变（c.318_319insT 和 c.922G>T），与 AT:A 降低有关。
