一个纤维蛋白原γ链Arg275His突变导致的遗传性异常纤维蛋白原血症家系

目的　对一个遗传性异常纤维蛋白原血症家系进行表型和基因型分析。方法　采集家系3代5人外周血,吸取上层血浆用血凝仪检测活化部分凝血酶原时间、凝血酶原时间、凝血酶时间、蛋白C活性、蛋白S活性和抗凝血酶活性,纤维蛋白原活性和抗原分别用Clauss法和免疫比浊法进行检测。以常规酚-氯仿法抽提家系所有成员外周血基因组DNA,PCR扩增纤维蛋白原基因FGA、FGB和FGG所有外显子及其侧翼序列,PCR产物纯化后直接测序以检测基因突变。结果　先证者活化部分凝血酶原时间、凝血酶原时间正常,凝血酶时间超出正常上限值2倍以上,纤维蛋白原活性明显下降,抗原也低于正常范围,且活性显著低于抗原;其母表型检测结果与之相似。基因分析显示先证者呈纤维蛋白原FGG基因第8外显子g.5 6 78G>A杂合碱基置换,导致Arg2 75 His错义突变,该突变来源于母系。结论　纤维蛋白原γ链Arg2 75 His杂合错义突变是引起该家系异常纤维蛋白原血症的原因。

Inherited dysfibrinogenemia caused by Arg275His in the γ chain of fibrinogen

OBJECTIVE: To analyze the phenotype and genotype of a family with inherited dysfibrinogenemia. METHODS: Laboratory tests including activated particle thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and the activity of protein C (PC), protein S(PS) and antithrombin (AT) were conducted in the proband and 4 family members. The activity and antigen of fibrinogen in plasma were measured by functional and immunoturbidimetry assay, respectively. All the exons and exon-intron boundaries of the three fibrinogen genes were analyzed by direct sequencing. RESULTS: The proband had normal APTT and PT, but prolonged TT. Her plasma fibrinogen levels were extremely reduced, which was also found in her mother. The sequencing results of the proband revealed heterozygous g.5678 G>A in the exon 8 of FGG gene originating from her mother, which caused Arg275His missense mutation. CONCLUSION: Dysfibrinogenemia in the family is caused by Arg275His in the beta chain of fibrinogen and it is the first report on a Chinese family with inherited dysfibrinogenemia.