三个遗传性异常纤维蛋白原血症家系的表型和基因型分析
Analysis of phenotype and genotype in three Chinese pedigrees with inherited dysfibrinogenemia
欧阳琦 1丁秋兰 2黄丹丹 1许冠群 2张利伟 2戴菁 2陆晔玲 2王学锋 2奚晓东 1王鸿利1
作者信息
- 1. 200025,上海交通大学医学院附属瑞金医院、上海血液学研究所,医学基因组学国家重点实验室
- 2. 上海交通大学医学院附属瑞金医院临床输血科
- 折叠
摘要
目的 对3个遗传性异常纤维蛋白原血症家系进行临床表型和基因型分析.方法 检测3个家系所有成员外周血活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、靳蛇酶时间(RT)、抗凝血酶活性(AT:C)、蛋白C活性(PC:C)和蛋白S活性(PS:C),纤维蛋白原(Fg)抗原和活性分别用免疫比浊法和Clauss法测定,分别用SDS-PAGE和Western blot法检测3例先证者血浆纤维蛋白原三条肽链的相对分子质量.抽提DNA,PCR扩增Fg 3个基因FGA、FGB和FGG所有外显子及其侧翼序列,DNA测序并进行基因分析.结果 3例先证者APTT、PT以及抗凝指标(AT:C、PC:C和PS:C)都正常,而TT和RT明显延长,Fg的活性降低,分别为0.90、0.84及0.44 g/L,而抗原正常,分别为2.0、3.2及3.1 g/L;SDS-PAGE和Western blot法均未检测到异常条带.基因分析发现3例先证者各携带1个杂合错义突变,分别为FGG g.7476 G→A(γ Arg275His)、FGA g.1209 C→T(Aα Pro18Leu)和FGA g.1202 C→T(Aα Arg16Cys).结论 3例先证者遗传性异常纤维蛋白原血症分别由γ Arg275 His、Aα Pro18Leu和Aα Arg16Cys突变所致,其中Aα Pro18Leu和Aα Arg16Cys突变为国内首次报道.
Abstract
Objective To analyze the phenotype and genotype in three Chinese pedigrees with inherited dysfibrinogenemia. Methods Laboratory tests including activated partial thromboplastin time (APTT) ,plasma fibrinogen(Fg) were analyzed by Clauss and immunoturbidimetry methods, respectively. The Fg of three probands was assessed by Western blot and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The sequences of all the exons and exon-intron boundaries of the three Fg genes FGA, GFB and FGG were amplified by PCR and analyzed by direct sequencing. Results Three probands had normal ma Fg were reduced, but antigen levels were normal. Western blot and SDS-PAGE showed no abnormal molecular weight of Fg. The 3 heterozygous mutations of γ Arg275His, Aα Pro18Leu and Aα Arg16Cys were identified in the 3 probands, respectively. Conclusion The three probands with dysfibrinogenemia were caused by the mutations of γ Arg275His, Aα Pro18Leu and Aα Arg16Cys, respectively. Both Aα Pro18Leu and Aα Arg16Cys were first reported in Chinese population.
关键词
异常纤维蛋白原血症,遗传性/纤维蛋白原/基因突变/表型和基因型Key words
Dysfibrinogenemia, inherited/Fibrinogen/Gene mutation/Phenotype and genotype引用本文复制引用
出版年
2011
NETL
NSTL
维普
万方数据