Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency

doi:10.3760/cma.j.issn.1003-9406.2013.03.014

科研成果详情

题名	Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency
其他题名	Identification of a novel mutation of factor Ⅻ gene in a family with coagulation FⅫ deficiency
作者	Haixiao Xie; Meiyan Lv; Xiaoli Yang; Liqing Zhu; Lihong Yang; Yanhui Jin; Mingshan Wang
发表日期	2013-06-01
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	英语
原始文献类型	Article
关键词	Coagulation factor XII F XII gene Mutant Polymerase chain reaction
其他关键词	Coagulation factor Ⅻ ; Polymerase chain reaction ; F Ⅻ gene ; Mutant
摘要	Objective: To analyze genetic mutation and molecular pathogenesis in a family affected with inherited coagulation factor XII(FXII) deficiency. Methods: Activated partial thromboplastin time (APTT), FXII procoagulant activity (FXII:C), FXII antigen (FXII:Ag) and other coagulants were measured. For affected members of the family, exons 1-14 and flanking intronic regions of the FXII gene were amplified with polymerase chain reaction (PCR) and sequenced thereafter. Expression plasmids containing mutant FXII cDNA was constructed and transfected into COS7 cells transiently. Expressions of FXII:Ag and FXII:C were analyzed. Results: The proband has manifested a prolonged APTT of 108.1 s (reference range: 27.0-41.0 s). Her husband has a normal APTT. Other members of the family had slightly increased APTT. The FXII:C and FXII:Ag of the proband have both dropped to about 0.01 (reference range: 0.72-1.13). The FXII:C levels of her husband, son, daughter and grandchild were 0.57, 0.24, 0.14, 0.16, respectively. And the FXII:Ag levels in her husband, son, daughter and grandchild were 0.55, 0.27, 0.15, 0.21, respectively. The proband and her daughter have both carried a heterozygous deletional mutation 6800-6808delAGCTGGGAG (6800-6808del9bp) in exon 9. For the promoter region of the FXII gene, the genotypes of the proband, her son, daughter and grandchild was TT, whilst that of her husband was CT. Expression study has shown that, whilst the mutant FXII protein has accumulated in the cells similar to wild-type protein, its secretion has reduced approximately by half. Conclusion: A novel deletional mutation 6800-6808del9bp has been identified in the FXII gene. Although mutant FXII protein can still accumulate in cells, its secretion has become insufficient. The 6800-6808del9bp mutation and 46T/T have both contributed to the pathogenesis of FXII deficiency in the family, but may have not been the sole cause.
其他摘要	Objective To analyze genetic mutation and molecular pathogenesis in a family affected with inherited coagulation factor Ⅻ (F Ⅻ) deficiency.Methods Activated partial thromboplastin time (APTT),FⅫ procoagulant activity (FⅫ ∶ C),FⅫ antigen (FⅫ ∶ Ag) and other coagulants were measured.For affected members of the family,exons 1-14 and flanking intronic regions of the FⅫ gene were amplified with polymerase chain reaction (PCR) and sequenced thereafter.Expression plasmids containing mutant FⅫ cDNA was constructed and transfected into COS7 cells transiently.Expressions of FⅫ ∶ Ag and FⅫ ∶ C were analyzed.Results The proband has manifested a prolonged APTT of 108.1 s (reference range:27.0-41.0 s).Her husband has a normal APTT.Other members of the family had slightly increased APTT.The FⅫ ∶ C and FⅫ ∶ Ag of the proband have both dropped to about 0.01 (reference range:0.72-1.13).The FⅫ ∶ C levels of her husband,son,daughter and grandchild were 0.57,0.24,0.14,0.16,respectively.And the FⅫ ∶ Ag levels in her husband,son,daughter and grandchild were 0.55,0.27,0.15,0.21,respectively.The proband and her daughter have both carried a heterozygous deletional mutation 6800-6808delAGCTGGGAG (6800-6808del9bp) in exon 9.For the promoter region of the FⅫgene,the genotypes of the proband,her son,daughter and grandchild was TT,whilst that of her husband was CT.Expression study has shown that,whilst the mutant F Ⅻ protein has accumulated in the cells similar to wild-type protein,its secretion has reduced approximately by half.Conclusion A novel deletional mutation 6800-6808de19bp has been identified in the FⅫ gene.Although mutant F Ⅻ protein can still accumulate in cells,its secretion has become insufficient.The 6800-6808del9bp mutation and 46T/T have both contributed to the pathogenesis of FⅫ deficiency in the family,but may have not been the sole cause.
资助项目	浙江省温州市科技计划项目
ISSN	1003-9406
卷号	30 期号:3 页码:313-7.
DOI	10.3760/cma.j.issn.1003-9406.2013.03.014
页数	5
收录类别	PUBMED ; SCOPUS ; CSCD ; 万方 ; ISTIC ; PKU ; 北大核心
学科领域	医药、卫生 ; 基础医学
URL	查看原文
CSCD记录号	CSCD:5028145
PubMed ID	23744322
SCOPUSEID	2-s2.0-84879848707
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/63703
专题	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
作者单位	Diagnosis Center of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
第一作者单位	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
第一作者的第一单位	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
推荐引用方式 GB/T 7714	Haixiao Xie,Meiyan Lv,Xiaoli Yang,et al. Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency[J]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics,2013,30(3):313-7..
APA	Haixiao Xie., Meiyan Lv., Xiaoli Yang., Liqing Zhu., Lihong Yang., ... & Mingshan Wang. (2013). Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 30(3), 313-7..
MLA	Haixiao Xie,et al."Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency".Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 30.3(2013):313-7..