[Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene]

doi:10.3760/cma.j.cn511374-20210407-00308

科研成果详情

题名	[Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene]
作者	Yingying Chen; Yating Yao; Ting Li; Kuangyi Shu; Xiao Yang; Shanshan Li; Xiaoou Wang; Jinyuan Wang; Ting Zhang; Minghua Jiang
发表日期	2024-03-10
发表期刊	Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 影响因子和分区
语种	中文
原始文献类型	English Abstract ; Journal Article
摘要	To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency., A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children's Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer. Antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) in plasma were determined with chromogenic substrate and immunonephelometry assays. All exons and flanking sequences of the anticoagulant protein gene SERPINC1 were amplified by PCR and subjected to Sanger sequencing. Candidate variants were verified with bioinformatic tools (PolyPhen-2, SIFT, Mutation Taster and PYMOL) to explore their effect on the function and structural conformation of the protein., The probands (II-2, II-10), their brother (II-5) and sons (III-1, III-8) had shown normal PT, APTT, FIB, and TT, but significantly decreased AT: A and AT: Ag, with their levels being 34%, 57%, 56%, 48%, 53% and 13.51 mg/dL, 13.44 mg/dL, 18.39 mg/dL, 17.36 mg/dL, 17.71 mg/dL, respectively. The remaining pedigree members had normal values. Sanger sequencing revealed that the probands and all affected pedigree members had harbored a heterozygous c.851T>C (p.Met284Thr) missense variant in exon 5 of the SERPINC1 gene. Bioinformatic analysis and simulation suggested that the variant has resulted in alteration of hydrogen bonds at the c.851 position, which may affect the structure of the protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS1+PM1+PM5+PP1+PP4)., The probands and other affected members were all diagnosed with type I hereditary AT deficiency, for which the c.851T>C (p.Met284Thr) variant of the SERPINC1 gene may be accountable.
ISSN	1003-9406
卷号	41 期号:3 页码:312-316
DOI	10.3760/cma.j.cn511374-20210407-00308
收录类别	PUBMED ; SCOPUS
URL	查看原文
PubMed ID	38448020
SCOPUSEID	2-s2.0-85187198575
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210217
专题	附属第二医院_耳鼻咽喉科
作者单位	Department of Otolaryngology, the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children's Hospital, Wenzhou, Zhejiang 325027, China. minghua93@126.com.
第一作者单位	附属第二医院_耳鼻咽喉科
第一作者的第一单位	附属第二医院_耳鼻咽喉科
推荐引用方式 GB/T 7714	Yingying Chen,Yating Yao,Ting Li,et al. [Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene][J]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics,2024,41(3):312-316.
APA	Yingying Chen., Yating Yao., Ting Li., Kuangyi Shu., Xiao Yang., ... & Minghua Jiang. (2024). [Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 41(3), 312-316.
MLA	Yingying Chen,et al."[Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene]".Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 41.3(2024):312-316.