Fang Yi, Wang Hong-Li, Wang Xue-Feng, Fu Qi-Hua, Wang Wen-Bin, Xie Shuang, Zhou Rong-Fu, Dai Jing, Wang Zhen-Yi
Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Second Medical University, Shanghai 200025, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Dec;13(6):1086-9.
Congenital afibrinogenemia is a rare autosomal recessive disorder, characterized by the complete absence or extremely reduced level of fibrinogen. To analyze the phenotype and genotype of a family with inherited afibrinogenemia, laboratory studies including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were tested in the proband and 9 family members. Fibrinogen (Fg) in plasma were measured by both functional and immunoturbidimetry assay. All the exons, exon-intron boundaries and promoter regions of three Fg genes were analyzed by direct sequencing. 102 healthy blood donors were used as normal control. The results showed that phenotype of the proband was diagnosed as afibrinogenemia. Compound heterozygous mutations in Fg FGB gene were detected in the proband. One was a nonsense mutation (Arg17stop) in exon 2, traced back to the proband's mother. The other was a missense mutation (Gly347Arg) in exon 7, which was from the proband' s father. It is concluded that afibrinogenemia is caused by the compound heterozygous mutations Arg17stop and Gly347Arg in the Beta beta-chain of fibrinogen.
先天性无纤维蛋白原血症是一种罕见的常染色体隐性疾病，其特征是纤维蛋白原完全缺失或水平极低。为分析一个遗传性无纤维蛋白原血症家族的表型和基因型，对先证者及9名家族成员进行了实验室检查，包括活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）和凝血酶时间（TT）。采用功能测定法和免疫比浊法检测血浆中的纤维蛋白原（Fg）。通过直接测序分析了三个Fg基因的所有外显子、外显子-内含子边界和启动子区域。选取102名健康献血者作为正常对照。结果显示，先证者的表型被诊断为无纤维蛋白原血症。在先证者中检测到Fg FGB基因的复合杂合突变。一个是外显子2中的无义突变（Arg17stop），追溯至先证者的母亲。另一个是外显子7中的错义突变（Gly347Arg），来自先证者的父亲。结论是，无纤维蛋白原血症是由纤维蛋白原β链中的复合杂合突变Arg17stop和Gly347Arg引起的。
