9例遗传性凝血因子Ⅶ缺陷症患者基因诊断与表型分析

发布时间：2018-01-06 00:32

本文关键词：9例遗传性凝血因子Ⅶ缺陷症患者基因诊断与表型分析　出处：《上海交通大学》2015年硕士论文　论文类型：学位论文

【摘要】：【目的】探讨9例遗传性凝血因子VII(FVII)缺陷症患者的基因突变类型与临床特征。【方法】采用一期法检测患者的FVII活性(FVII:C),用双抗体夹心酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测其FVII抗原(FVII:Ag)水平;并抽提患者的外周血基因组DNA,PCR扩增FVII基因所有外显子及其侧翼序列,采用DNA直接测序进行基因分析。【结果】在9例遗传性FVII缺陷症患者中发现10种基因突变,包括3种剪切位点突变和7种错义突变,其中p.Gly406(346)Asn、c.*64GA、p.Ile213(153)Asn这3种突变为国际首次报道。1例患者为p.Tyr128(68)Cys纯合突变,其FVII:C为0.8%,FVII:Ag为2.5%,临床表型为反复重度出血;5例患者携带FVII基因双杂合突变,分别为p.Thr241(181)Asn和p.Gly406(346)Asn、IVS1a+5GA和p.His408(348)Gln、IVS5-1GA和p.His408(348)Gln、c.*64GA合并p.Ile213(153)Asn、p.Cys389(329)Gly和p.His408(348)Gln的双杂合突变,其相应的FVII:C分别为1.2%、4.4%、1.0%、0.5%和1.2%,患者临床出血症状轻重不一。3例患者携带杂合突变,分别p.Cys389(329)Gly、p.His408(348)Gln和p.Thr419(359)Met,其FVII:C分别为0.5%、8.3%和9.4%,第一位有出血史,后两位无明显出血。【结论】在9例遗传性FVII缺陷症患者中发现了10种基因突变,其中3种为新发现突变。p.His408(348)Gln突变较常见,而FVII:C与患者的临床表型间无相关性。
[Abstract]:[objective] to investigate the gene mutation types and clinical characteristics of 9 patients with hereditary coagulation factor VIIF FVIIdeficiency. [methods] the activity of FVII was detected by one-stage method. . Enzyme-linked immunosorbent assay was detected by double antibody sandwich enzyme-linked immunosorbent assay (Elisa). The level of FVII antigen FVII: Agwas detected by Elisa. All exons and flanking sequences of FVII gene were amplified by PCR. DNA sequencing was used for gene analysis. [results] Ten gene mutations were found in 9 patients with hereditary FVII deficiency, including 3 splicing site mutations and 7 missense mutations. Among them, p. Gly406, 346A, Asnnchus c. Y64GA. It is the first time in the world that P. Ile213A153An mutation is a homozygous mutation of p. Tyr128t68Cys with a FVII:C of 0.8%. The FVII:Ag was 2.5% and the clinical phenotype was recurrent severe hemorrhage. Five patients carried double heterozygous mutations of FVII gene, which were p.Thr241n181Asn and p.Gly406C346An, respectively. IVS1a 5GA and p.His408C348GN IVS5-1GA and p.His408C348GN. The double heterozygous mutations of Cys389 / 329Gly and p. His408 / 348GN were found in C. Cai64GA combined with p. Ile213A153An Asnngly p.Cys389 / 329Gly and p. His408 / 348GN respectively. The corresponding FVII:C was 1.2% and 1.4%, respectively, and 0.5% and 1.2%, respectively. The patients with different clinical bleeding symptoms were carrying heterozygous mutations. The FVII:C of p. Cys389 and P. Thr419 was 0.5%, respectively. In 8.3% and 9.4, the first had a history of bleeding, and the last two had no significant bleeding. [conclusion] Ten gene mutations were found in 9 patients with hereditary FVII deficiency. Three of them were newly discovered mutations. P. His408C348GN mutation was more common, but there was no correlation between FVII:C and the clinical phenotype of the patients.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R554;R440

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