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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 diagnose hereditary factor V (FV) deficiency. Methods The clinical phenotypes of APLT, PT, FV: C and FV: Ag in probands and their pedigrees were detected by detecting the phenotypes of probands and their families. The 25 exons and their flanking sequences of F5 gene of proband were amplified by polymerase chain reaction (PCR). The PCR products were directly sequenced to find out the gene mutation and a pedigree investigation was conducted to find out the genetic law. Results proband APTT and PT were significantly prolonged, FV: C was 3.5%, FV: Ag was 1.47%. F5 gene sequencing found that proband F5 gene exon region has 7 different sites with the GenBank AY364535 sequence, including exon 10 C38591T heterozygous mutation resulting in a stop codon (R506Term), exons The homozygous C47504T mutation in region 13 led to the substitution of the encoded amino acid L1369F, which was confirmed as a genetic polymorphism. Pedigree analysis showed that the former inherited from the proband’s mother, the latter inherited from their parents. Conclusion Phenotypic testing, pedigree investigation and gene diagnosis confirm that the first symptom is hereditary coagulation factor V deficiency, and the termination codon of C38591T heterozygous mutation is one of the causes of FV deficiency in probands.