中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2015年
18期
1401-1404
,共4页
李芮冰%张蔓丽%王正冠%刘萍%段晋燕%王成彬%卢彦平
李芮冰%張蔓麗%王正冠%劉萍%段晉燕%王成彬%盧彥平
리예빙%장만려%왕정관%류평%단진연%왕성빈%로언평
因子Ⅶ缺乏%突变%序列分析,DNA
因子Ⅶ缺乏%突變%序列分析,DNA
인자Ⅶ결핍%돌변%서렬분석,DNA
Factor Ⅶ deficiency%Mutation%Sequence analysis,DNA
目的 对1例遗传性凝血因子(FⅦ)缺乏症患者进行F7基因分析,初步探讨其发病机制.方法 用DNA直接测序法分析患者F7基因的启动子、外显子及侧翼、3'非翻译区以及内含子7的重复序列突变位点区域,用反向测序证实所发生的突变.查找数据库和当地150名健康对照者相应序列,确定是否为常见SNP位点.结果 Sanger测序发现该患者F7基因内含子6发生g.15975 G＞A杂合突变(IVS6-1 G＞A),内含子7发生g.16813 A＞G多态性突变(IVS7+7 A＞G).15975位核苷酸发生G＞A突变后,内含子5的3'端剪接受体位点不能被识别,最近的候选剪接受体位点位于下游的132 bp处,由此推测IVS6-1G＞A突变后,导致外显子6丢失,从而影响FⅦ蛋白的合成分泌及功能.IVS7+7 A＞G多态性突变不引起剪接位点变化,文献报道其会影响蛋白之间相互作用,降低血浆FⅦ活性.结论 F7基因的IVS6-1G＞A杂合突变复合IVS7+7 A＞G突变是导致该患者凝血因子Ⅶ下降的原因.
目的 對1例遺傳性凝血因子(FⅦ)缺乏癥患者進行F7基因分析,初步探討其髮病機製.方法 用DNA直接測序法分析患者F7基因的啟動子、外顯子及側翼、3'非翻譯區以及內含子7的重複序列突變位點區域,用反嚮測序證實所髮生的突變.查找數據庫和噹地150名健康對照者相應序列,確定是否為常見SNP位點.結果 Sanger測序髮現該患者F7基因內含子6髮生g.15975 G＞A雜閤突變(IVS6-1 G＞A),內含子7髮生g.16813 A＞G多態性突變(IVS7+7 A＞G).15975位覈苷痠髮生G＞A突變後,內含子5的3'耑剪接受體位點不能被識彆,最近的候選剪接受體位點位于下遊的132 bp處,由此推測IVS6-1G＞A突變後,導緻外顯子6丟失,從而影響FⅦ蛋白的閤成分泌及功能.IVS7+7 A＞G多態性突變不引起剪接位點變化,文獻報道其會影響蛋白之間相互作用,降低血漿FⅦ活性.結論 F7基因的IVS6-1G＞A雜閤突變複閤IVS7+7 A＞G突變是導緻該患者凝血因子Ⅶ下降的原因.
목적 대1례유전성응혈인자(FⅦ)결핍증환자진행F7기인분석,초보탐토기발병궤제.방법 용DNA직접측서법분석환자F7기인적계동자、외현자급측익、3'비번역구이급내함자7적중복서렬돌변위점구역,용반향측서증실소발생적돌변.사조수거고화당지150명건강대조자상응서렬,학정시부위상견SNP위점.결과 Sanger측서발현해환자F7기인내함자6발생g.15975 G＞A잡합돌변(IVS6-1 G＞A),내함자7발생g.16813 A＞G다태성돌변(IVS7+7 A＞G).15975위핵감산발생G＞A돌변후,내함자5적3'단전접수체위점불능피식별,최근적후선전접수체위점위우하유적132 bp처,유차추측IVS6-1G＞A돌변후,도치외현자6주실,종이영향FⅦ단백적합성분비급공능.IVS7+7 A＞G다태성돌변불인기전접위점변화,문헌보도기회영향단백지간상호작용,강저혈장FⅦ활성.결론 F7기인적IVS6-1G＞A잡합돌변복합IVS7+7 A＞G돌변시도치해환자응혈인자Ⅶ하강적원인.
Objective The identify the gene defect of an inherited FⅦ deficiency patient.Methods The promoter,all the exons and exon-intron boundaries and 3' UTR of F7 gene of the proband were analyzed by direct sequencing.The defected mutations were confirmed by sequencing the complementary strand.The mutations would be screened in the related database and 150 healthy donors to identify the SNP.By splice site prediction,we analyzed the pathogenesis of defected mutations.Results Genetic analysis revealed G to A transition at 15975 in the intron 6 of F7gene (IVS6-1 G ＞ A)and A to G transition at 16813 in the intron 7 of F7 gene (IVS7 +7 A ＞ G).According to the fruitfly,the acceptor site could not be recognized when a G to A substitution took place.The closest candidate splice site was located 132 bp downstream.The distance was probably too far to allow the use of the cryptic splice site and resulted in the skipping of exon6.A to G transition at 16813 in the intron 7 of F7 gene could not change the splice site,but modify a different molecular interaction that is important for the splice process.Conclusion The heterozygous mutation of IVS6-1G ＞ A combined with polymorphism of IVS7 + 7 A ＞ G in F7 gene relates to the FⅦ deficiency.
