摘要
目的对遗传性凝血因子V(FV)缺陷症进行诊断。方法通过检测先证者及家系成员的活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、FV促凝活性(FV∶C)和FV抗原(FV∶Ag)等进行临床表型诊断,应用聚合酶链反应(PCR)方法对先证者F5基因的25个外显子及其侧翼序列进行扩增,PCR产物进行直接测序以发现其基因突变,进行家系调查以期发现遗传规律。结果先证者APTT和PT显著延长,FV∶C为3.5%,FV∶Ag为1.47%。F5基因测序发现,先证者F5基因外显子区共有7处与GenBank AY364535序列不同的位点,其中外显子10区的C38591T杂合突变导致产生1个终止密码(R506Term),外显子13区的C47504T纯合变异导致编码氨基酸L1369F替换,该变异被证实为基因多态性。家系分析表明,前者遗传于先证者母亲,后者遗传于其父母双亲。结论通过表型检测、家系调查和基因诊断,明确该先症者为遗传性凝血因子V缺陷症,C38591T杂合突变产生终止密码是导致先证者FV缺陷的原因之一。
Objective To study on the laboratory diagnosis of a patient with inherited coagulation factor V （FV） deficiency. Methods The activated partial thromboplastin time （APTF） , prothrombin time （PT） , FV activity （FV： C） and FV antigen（FV：Ag） were used for phenotype diagnosis. 25 exons and their flanks of F5 gene were amplified from the proband＇s genomie DNA by polymerase chain reaction（ PCR）, PCR products were directly sequenced to analyze the F5 gene mutation. Results The proband showed significantly prolonged APTT and PT values, FV：C and FV：Ag were 3.5% and 1.47% respectively. Comparing with GenBank AY364535 sequence,seven variants have been found in F5 exons by DNA sequencing. C38951T heterozygous mutation in exon 10 introduce a stop code at 506 amino acid position（R506Term） , and C47504T homozygous variant cause Lys to Phe substitution at 1369 amino acid position,which has been confirmed as a gene polymorphism. Pedigree analysis results revealed that the former mutation was inherited from proband＇s father and the latter was from her parents. Conclusions Phenotype diagnosis and gene analysis results indicated that this was a patient with inherited FV deficiency. 175 gene C38951T heterozygous mutation which introduced a stop code was the partial mechanism causing FV deficiency for this proband.
出处
《检验医学》
CAS
北大核心
2008年第6期600-603,共4页
Laboratory Medicine
关键词
凝血因子V缺陷症
表型
基因
突变
诊断
Coagulation factor V deficiency
phenotype
Gene
Mutation
diagnosis
