Fang Y, Dai B-T, Wang X-F, Fu Q-H, Dai J, Xie F, Cai X-H, Wang H-L, Wang Z-Y
Division of Thrombosis and Hemostasis, Shanghai Institute of Hematology, Ruijin Hospital, Medical College of Shanghai Jiao Tong University, Shanghai, China.
Haemophilia. 2006 Nov;12(6):615-20. doi: 10.1111/j.1365-2516.2006.01320.x.
Congenital afibrinogenaemia is a rare autosomal recessive disorder, characterized by the complete absence or extremely reduced level of fibrinogen (Fg). We attempted to analyse the phenotype and genotype in two Chinese families with congenital afibrinogenaemia. Coagulation studies including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) and Fg were performed in the patients and other family members. All the exons, exon-intron boundaries and promoter regions of three Fg genes (FGA, FGB and FGG) were screened by direct sequencing. Three patients in two families suffered from moderate to severe haemorrhage. Their APTT, PT and TT were extremely prolonged and plasma Fg levels were undetectable by Clauss method and extremely reduced by immunoassay. Genetic analysis revealed three FGA mutations in three patients including one novel mutation. In family 1, patient 1 was detected compound heterozygous mutations in FGA, g.1892-1899delAGTA/GTAA from her patriline and g.1978-g.3215del1238 bp from her matriline. In family 2, a homozygous Gln203X in Aalpha-chain was found in both patients 2 and 3 due to consanguineous marriage. All these mutations were null mutations, which could produce premature stop codons in FGA. It can be indicated that with more genetic analysis performed on afibrinogenaemia patients all over the world, there is no distinct difference in geographical distribution of Fg gene mutations. Gln203X in Aalpha-chain was first reported in this study, which may help to further understand the function of Aalpha-chain.
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（Fg）完全缺失或水平极低。我们试图分析两个先天性无纤维蛋白原血症中国家系的表型和基因型。对患者及其他家庭成员进行了包括活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、凝血酶时间（TT）及Fg在内的凝血研究。通过直接测序对三个Fg基因（FGA、FGB和FGG）的所有外显子、外显子 - 内含子边界及启动子区域进行筛查。两个家系中的三名患者有中度至重度出血症状。他们的APTT、PT和TT极度延长，用Clauss法检测血浆Fg水平无法测出，免疫测定法显示其水平极低。基因分析在三名患者中发现了三个FGA突变，其中包括一个新突变。在家族1中，患者1被检测到FGA存在复合杂合突变，父系遗传的g.1892 - 1899delAGTA/GTAA和母系遗传的g.1978 - g.3215del1238 bp。在家族2中，由于近亲结婚，患者2和患者3均发现Aα链上存在纯合的Gln203X突变。所有这些突变均为无效突变，可在FGA中产生过早的终止密码子。可以表明，随着对世界各地无纤维蛋白原血症患者进行更多的基因分析，Fg基因突变的地理分布没有明显差异。本研究首次报道了Aα链上的Gln203X突变，这可能有助于进一步了解Aα链的功能。
