女性A型血友病F基因突变分析  

Gene Mutation Analysis of Coagulation Factor Ⅷfrom a Female Patient with Hemophilia A

作　　者：周静[1] 闫乃红[2] 贾永前[1] 卢亦路[2] 余江[1] 曹桂群[2] 陈清英[2] 王玲[2] 张发强[2] 夏庆杰[2] 

机构地区：[1]四川大学华西医院实验医学科临检血液室,成都610041 [2]四川大学华西医院眼疾病分子遗传研究室

出　　处：《四川大学学报（医学版）》2006年第3期492-494,共3页Journal of Sichuan University(Medical Sciences)

摘　　要：报道罕见的女性A型血友病1例,并对其凝血因子进行基因突变分析。患者,女,65岁,因为跌倒后右胸痛2d入院,院内查体提示胸壁皮下血肿,双下肢等长,髋屈曲及内旋受限。测定凝血指标提示APTT61.3s,正常血浆纠正后为41.3s,而PT、FIB、TT均正常。有既往出血史。F活性为2%,F活性为200%,vWF:Ag为120%,vWF:RCof100%,vWF:CBA128%,F结合分析正常;髋关节X片提示:双侧髋臼发育不良,髋关节骨关节炎。临床诊断为血友病A型。提取该患者外周血DNA,根据NM000132之凝血因子F基因序列设计合成了其第14外显子特异的引物,行聚合酶链反应扩增,并对扩增产物进行测序分析,测序结果与标准序列进行比较,发现该患者出现4111A→C杂合突变,使1314位氨基酸由苏氨酸变为脯氨酸,产生一错意突变,该突变未见其它文献报道。Hemophilia A affects male, whereas females are carriers and generally spared from this disease. However, we here reported a 65-year-old female with Hemophilia A while screening the gene mutation of coagulation factor Ⅷ. The female went to hospital because of tripping to lead her right chest to be injured with subcutaneous hematoma. She had historically a hemorrhagic diathesis. The physical examination discovered her hip limited to bend and move, but no discrepancy length between her two legs. The initial laboratory tests showed that the activated partial thromboplastin time （APTT） was 61. 3 seconds （20-40 seconds）, and the APTT corrected by mixing with normal plasma was 41.3 s, but the levels of PT, FIB and TT were normal. The plain radiographs revealed the hip joints to suffer from the acetabular dysplasia and osteoarthritis. The level of FⅧ ：C was 2%, F Ⅸ ：C 200%, vWF：Ag 120%, vWF：Rcof 100%, vWF：CBA 128%, and the FⅧ binding assay to vWF was normal. The primers for exon 14 of FⅧ gene were designed according to the NM _ 000132 gene sequence. DNA was abstracted from the patient blood. PCR were carried out and the DNA sequence was followed. A new mutation of 4111A→C was discovered, which caused the amino acid sequence changed （T 1314 P）. The mutation of T 1314 P may be the cause of this female patient to get the hemophilia A. This mutation was a novel one which has never been reported before.

关 键 词：A型血友病 凝血因子FⅧ 基因突变 女性 

分 类 号：R55[医药卫生—血液循环系统疾病]