Congenital hypodysfibrinogenemia associated with a novel deletion of three residues (gamma Ala289_Asp291del) in fibrinogen

doi:10.1007/s11239-018-1678-2

科研成果详情

题名	Congenital hypodysfibrinogenemia associated with a novel deletion of three residues (gamma Ala289_Asp291del) in fibrinogen
作者	Zhu, Liqing1; Zhao, Misheng 2; Wang, Mingshan1; Lou, Zhefeng3; Chen, Xiaoli 1; Pan, Liangliang3; Yu, Dandan 1; Xia, Wenli 2; Wang, Han 2; Zhou, Bin 4; Gao, Shenmeng4
发表日期	2018-08
发表期刊	JOURNAL OF THROMBOSIS AND THROMBOLYSIS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Fibrinogen Amino acid deletion Hypodysfibrinogenemia Fibrin polymerization Fibrin clot formation Fibrinolysis
其他关键词	DOMAIN CAUSES HYPOFIBRINOGENEMIA ; POLYMERIZATION ; SUBSTITUTION ; MUTATION ; FEATURES
摘要	Hypodysfibrinogenemia is the least frequently reported congenital fibrinogen disorder, characterized by both quantity and quality defects of fibrinogen. In this study, we investigated the molecular basis of hypodysfibrinogenemia in a Chinese family. Functional fibrinogen was measured by Clauss method, and the antigenic fibrinogen was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of fibrinogen genes (FGA, FGB and FGG) were analysed by direct DNA sequencing. To further evaluate its molecular and functional characterizations, fibrinogen was purified from the plasma of propositus, then SDS-PAGE, fibrin polymerization, clot lysis, and electron microscopy scanning were all performed. The propositus showed a slight decrease of immunologic fibrinogen (1.52 g/L) but dramatically reduced functional fibrinogen (0.3 g/L). DNA sequencing revealed a novel heterozygous CCTTTGATG deletion in the exon 8 of FGG, leading to the deletion of Ala289, Phe290, and Asp291 in fibrinogen gamma-chain. The polymerization of the fibrinogen from the propositus was markedly impaired, with prolonged lag period and decreased final turbidity. The fibrinogen clottability showed a reduced fraction of participating clot formation. While the clot lysis showed normal. Scanning electron microscopy revealed that the fibers of the propositus were thicker than normal, with larger pores and curlier meshworks. We conclude that gamma Ala289_Asp291del is responsible for the hypodysfibrinogenemia in this case.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81501810, 81672087]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ15H200001]
出版者	SPRINGER
出版地	DORDRECHT
ISSN	0929-5305
EISSN	1573-742X
卷号	46 期号:2 页码:211-218
DOI	10.1007/s11239-018-1678-2
页数	8
WOS类目	Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
WOS研究方向	Cardiovascular System & Cardiology ; Hematology
WOS记录号	WOS:000439347100012
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	29748775
SCOPUSEID	2-s2.0-85046756312
通讯作者地址	[Gao, Shenmeng]Department of Internal Medicine,The First Hospital of Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China
Scopus学科分类	Hematology;Cardiology and Cardiovascular Medicine
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/15262
专题	附属第一医院检验医学院（生命科学学院、生物学实验教学中心）第一临床医学院（信息与工程学院）、附属第一医院_临床检验诊断学
通讯作者	Gao, Shenmeng
作者单位	1.Department of Clinical Laboratory,The First Hospital of Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China; 2.Department of Clinical Laboratory,Wenzhou People’s Hospital,Lucheng District,Wenzhou,325000,China; 3.School of Laboratory Medicine and Life Science,Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China; 4.Department of Internal Medicine,The First Hospital of Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Zhu, Liqing,Zhao, Misheng,Wang, Mingshan,et al. Congenital hypodysfibrinogenemia associated with a novel deletion of three residues (gamma Ala289_Asp291del) in fibrinogen[J]. JOURNAL OF THROMBOSIS AND THROMBOLYSIS,2018,46(2):211-218.
APA	Zhu, Liqing., Zhao, Misheng., Wang, Mingshan., Lou, Zhefeng., Chen, Xiaoli., ... & Gao, Shenmeng. (2018). Congenital hypodysfibrinogenemia associated with a novel deletion of three residues (gamma Ala289_Asp291del) in fibrinogen. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, 46(2), 211-218.
MLA	Zhu, Liqing,et al."Congenital hypodysfibrinogenemia associated with a novel deletion of three residues (gamma Ala289_Asp291del) in fibrinogen".JOURNAL OF THROMBOSIS AND THROMBOLYSIS 46.2(2018):211-218.