1例SERPINC1基因p.G180E变异致复发性流产分析  

Analysis of a case with recurrent spontaneous abortion caused by a variant of p.G180E in SERPINC1 gene

作　　者：林国 章林华 谢耀盛[2] 谢海啸[2] LIN Guo;ZHANG Linhua;XIE Yaosheng;XIE Haixiao(The People’s Hospital of Yuhuan,Taizhou,Zhejiang 317600,China;The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325015,China)

机构地区：[1]玉环市人民医院,浙江台州317600 [2]温州医科大学附属第一医院医学检验中心,浙江温州325015

出　　处：《中国优生与遗传杂志》2023年第11期2291-2294,共4页Chinese Journal of Birth Health & Heredity

基　　金：温州市科技计划基金项目(Y20220126)。

摘　　要：目的 对1个SERPINC1基因杂合变异导致遗传性抗凝血酶(AT)缺陷症家系进行表型和基因型分析,探讨变异基因与复发性流产的关系。方法 家系3代共7人,检测其AT活性(AT activity,AT:A)和AT抗原(AT antigen,AT:Ag)等指标,并提取相应外周血DNA进行PCR扩增测序。用在线生物信息软件分析氨基酸变异位点的保守性(ClustalX-2.1-win软件),分析变异对蛋白质功能的影响(PolyPhen-2、PROVEAN、SIFT和Mutation Taster软件),并对变异位点进行蛋白模型分析(PyMol软件)。结果 先证者的AT:A和AT:Ag分别为53%和154 mg/L,其父亲分别为51%和148 mg/L。DNA测序分析发现先证者及其父亲的SERPINC1基因第3号外显子均存在c.539G>A杂合错义变异(p.Gly180Glu)。保守性分析表明p.Gly180在10种同源物种间高度保守;4个在线生物信息学软件预测均显示p.Gly180Glu为致病变异;蛋白模型分析显示p.Gly180Glu变异使其侧链延长导致分子量增加从而改变蛋白质空间构象。结论 该家系SERPINC1基因第3号外显子c.539G>A(NM_000488)杂合错义变异(p.Gly180Glu)与其AT水平减低有关,可能也是先证者出现复发性流产的主要原因之一。Objective To analyze the phenotype and genotype of a heterozygous variant in the SERPINC1 gene and explore the relationship between the variant gene and recurrent abortion.Methods There were 3 generations including 7 persons.AT activity(AT activity,AT:A)and AT antigen(AT antigen,AT:Ag)were detected in the probands and their family members.Peripheral blood genomic DNA was extracted for DNA sequencing.The conservation of amino acid variation sites was analyzed by ClustalX-2.1-win software.The effect of variants on protein function was analyzed by PolyPhen-2,PROVEAN,SIFT and Mutation Taster,and the protein model of the variant sites was analyzed by PyMol software.Results The proband’s AT:A was 53%and AT:Ag was 154 mg/L respectively.The results of the father were 51%and 148 mg/L respectively.DNA sequencing analysis revealed that there was a c.539G>A heterozygous missense variant(p.Gly180Glu)in the gene of the proband and the father.The conservation analysis suggested that p.Gly180 was high conserved among 10 homologous species.All four online bioinformatics software predictions showed that p.Gly180Glu was a pathogenic variant.Protein model analysis revealed that the p.Gly180Glu variant extended its side chain to increase the molecular weight and thus changed the protein spatial conformation.Conclusion SERPINC1 gene c.539G>A(p.Gly180Glu)(NM_000488)heterozygous missense variant was related to its reduced AT level and might also be one of the main reasons for recurrent abortion in the proband.

关 键 词：遗传性抗凝血酶缺陷症 基因变异 复发性流产 血栓形成 

分 类 号：R714.21[医药卫生—妇产科学]