一个纤维蛋白原α链Arg 19 Gly突变导致的遗传性异常纤维蛋白原血症家系

Inherited Dysfibrinogenemia Caused by Arg19Gly in theαChain of Fibrinogen

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。方法采集先证者及其父母外周血进行常规出凝血检查,用Clauss法和免疫比浊法分别检测纤维蛋白原(Fbg)活性和抗原。抽提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,DNA测序并与基因文库比对确定基因异常。结果先证者活化部分凝血酶原时间(aPTT)、凝血酶原时间(PT)正常,凝血酶时间(TT)为28.10 s,Fbg活性明显下降,抗原在正常范围内,活性显著低于抗原;其父表型检测结果与之相似。基因分析发现,先证者及其父亲Fbg、FGA基因第2外显子均存在A1211G杂合碱基置换,导致Arg19Gly错义突变。结论鉴定该病例为遗传性异常纤维蛋白原血症,Fbgα链Arg19Gly杂合错义突变是致病原因。

Objective To analyze the phenotype and genotype of a family with inherited dysfibrinogenemia. Methods Venous blood samples were collected from the proband and his siblings, and routine coagulation tests were conducted. The activity and antigen of fibrinogen in plasma were measured by functional and immunoturbldlmetry assay, respectively. All the exons and exonintron boundaries of the three fibrinogen genes were analyzed by direct sequencing. Results The proband had normal activated partial thromboplastin time （aFFF） and prothrombin time （PT）, but prolonged thrombin time （28.10 s）. His plasma fibrinogen antigen was normal, but fibrinogen activity level was reduced （0.7g/L）, which was also found in his father. The sequencing results of the proband revealed heterozygous A1211G in the exon 2 of FGA gene originating from his father, which caused Arg19Gly missense mutation. Conclusion Dysfibrinogenemia in the family is caused by Arg19Gly in the α chain of fibrinogen and it is the second report on a Chinese family with inherited dysfibrinogenemia.