1例Aα链Arg16突变所致遗传性异常纤维蛋白原血症家系研究

Genetic Analysis of A Case of Congenital Dysfibrinogenemia Caused by Arg16His Mutation in Exon 2 of FGA

目的:1例遗传性异常纤维蛋白原血症家系的表型及基因型分析。方法:用血凝仪检测凝血指标,Clauss法检测纤维蛋白原活性,血浆蛋白电泳检测纤维蛋白原含量,Native-PAGE检测血浆纤维蛋白原及其片段分布,应用PCR扩增纤维蛋白原基因FGA、FGB和FGC所有外显子及其侧翼序列,PCR产物纯化后直接测序并进行基因分析。结果:先证者APTT正常,PT、TT明显延长;纤维蛋白原含量正常而活性降低,先证者姊妹及其女儿的检测结果与之相似,患者配偶所有指标均正常。基因分析显示,先证者纤维蛋白原FGA基因2号外显子g1233一a杂合碱基改变(密码子CGT→CAT),导致了Arg16His错义突变,该突变来源于父系。结论:该错义突变是导致遗传性异常纤维蛋白原血症的原因。

Objective： To analyze the phenotype and genotype of a family with congenital dysfibrinogenemia.Methods： Assays of coagulation,including activated partial thromboplastin time（APTT）,pro-thrombin time（PT） and thrombin time（TT） were carried out with Sysmex CA-7000 in the proband and his family members. The quality and quantity of fibrinogen in plasma were determined by Clauss and electrophoresis, respectively. Fibrinogen and inconstituent were analyzed by Native-PAGE. All exon and exon intron boundaries of fibringen genes were analyzed by direct sequencing. Results： The proband had normal APTT,but prolonged PT and TT. The activity of fibrinogen in plasma was decreased while its quantity was normal. These abnormalities were also found in his sisters and daughter,while his wife was normal. Genetic analysis revealed heterozygous G1233A in the exon 2 of FGA which resulted in Arg16His missense mutation. Conclusion： Inherited dysfibrinogenemia is caused by Arg16His mutation in exon 2 of FGA.