Luo Junfu, Zhang Wenwen, Zeng Qingfu, Zhou Weimin, Cao Qing, Zhou Wei
Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Key Laboratory of Molecular Medicine of Jiangxi Province, Nanchang, Jiangxi, China.
Eur J Med Genet. 2018 Feb;61(2):68-71. doi: 10.1016/j.ejmg.2017.10.019. Epub 2017 Nov 7.
Deep venous thrombosis (DVT) remains a serious clinical problem that affects millions of people worldwide. Some DVT cases are caused by inherited thrombophilia derived from genetic aberrations and several disease-causing genes have been identified so far. Among them, HRG is an uncommon one with limited related reports. Here, we reported on a family with early-onset DVT where acquired risky conditions were excluded. Whole exome sequencing revealed a novel heterozygous single base pair substitution in exon 2 of HRG gene resulting in a conserved residue replacement of the protein (c. C271T, p. P73S). Sanger sequencing confirmed the co-segregation of the mutation and plasma quantification determined circulating protein deficiency. The mutation might therefore impair hemostatic balance by causing reduced circulating HRG level. Our study broadens the mutation spectrum of the HRG gene and underscores the importance of its function in regulating coagulation pathway.
深静脉血栓形成（DVT）仍然是一个严重的临床问题，影响着全球数百万人。一些DVT病例是由遗传畸变导致的遗传性血栓形成倾向引起的，目前已经鉴定出了几种致病基因。其中，HRG是一种罕见的基因，相关报道有限。在此，我们报告了一个早发性DVT家族，排除了获得性风险因素。全外显子组测序揭示了HRG基因外显子2中一个新的杂合单碱基对替换，导致该蛋白的一个保守残基被替换（c.C271T，p.P73S）。桑格测序证实了该突变的共分离，血浆定量分析确定循环蛋白缺乏。因此，该突变可能通过降低循环HRG水平而损害止血平衡。我们的研究拓宽了HRG基因的突变谱，并强调了其在调节凝血途径中的功能的重要性。
