CAJ | 학술논문

目的研究4个遗传性凝血因子Ⅶ(FⅦ)缺陷症家系的临床表型及基因突变.方法用一期法测定先证者及其家系成员的凝血酶原时间(PT)及FⅦ活性(FⅦ:C),用双抗夹心ELISA测定血浆中FⅦ抗原(FⅦ:Ag),用PCR结合测序分析各家系成员的基因突变情况.结果各家系先证者PT明显延长,FⅦ:C与FⅦ:Ag明显降低.家系1先证者FⅦ基因为18041T→G纯合性突变,使未成熟FⅦ(ProFⅦ)的408位组氨酸(His)变为谷氨酸(Gln)(成熟蛋白的His348Gln);家系2先证者FⅦ基因测序发现5078-5079 CT双碱基的纯合性缺失,致使阅读框改变,在ProFⅦ的N端25位提前终止;家系3先证者FⅦ基因分析发现15975G→A与18093C→T双重杂合突变,前者为内含子6的3'端剪接位点突变(IVS6-1G→A),后者为无义突变,致使ProFⅦ蛋白的426位提前终止;家系4先证者FⅦ基因测序发现15975G→A与17908G→A双重杂合突变,后者使ProFⅦ364位Arg→Gln.结论在4个遗传性FⅦ缺陷症家系中发现His408Gln与5078-5079 del CT两个纯合突变及IVS6-1G→A、Gln426stop与IVS6-1G→A、Arg364Gln两个双重杂合突变.其中His408Gln与5078-5079 del CT为国内首次报道的纯合突变,IVS6-1G→A、Gln426stop为国际首次报道的突变.
목적 연구4개유전성응혈인자Ⅶ(FⅦ)결함증가계적림상표형급기인돌변.방법 용일기법측정선증자급기가계성원적응혈매원시간(PT)급FⅦ활성(FⅦ:C),용쌍항협심ELISA측정혈장중FⅦ항원(FⅦ:Ag),용PCR결합측서분석각가계성원적기인돌변정황.결과 각가계선증자PT명현연장,FⅦ:C여FⅦ:Ag명현강저.가계1선증자FⅦ기인위18041T→G순합성돌변,사미성숙FⅦ(ProFⅦ)적408위조안산(His)변위곡안산(Gln)(성숙단백적His348Gln);가계2선증자FⅦ기인측서발현5078-5079 CT쌍감기적순합성결실,치사열독광개변,재ProFⅦ적N단25위제전종지;가계3선증자FⅦ기인분석발현15975G→A여18093C→T쌍중잡합돌변,전자위내함자6적3'단전접위점돌변(IVS6-1G→A),후자위무의돌변,치사ProFⅦ단백적426위제전종지;가계4선증자FⅦ기인측서발현15975G→A여17908G→A쌍중잡합돌변,후자사ProFⅦ364위Arg→Gln.결론 재4개유전성FⅦ결함증가계중발현His408Gln여5078-5079 del CT량개순합돌변급IVS6-1G→A、Gln426stop여IVS6-1G→A、Arg364Gln량개쌍중잡합돌변.기중His408Gln여5078-5079 del CT위국내수차보도적순합돌변,IVS6-1G→A、Gln426stop위국제수차보도적돌변.
Objective To investigate the clinical manifestation and gene mutation in four Chinese pedigrees with the congenital coagulation factor Ⅶ deficiency. Methods Prothrombin time (PT), activated partial thromboplastin time, thrombin time and plasma fibrinogen were measured using STAGO STA-R automatic coagulation analyzer, and the coagulation activity of factor Ⅶ (FⅦ: C) was determined by a PT-based one stage method, and factor Ⅶ antigen (FⅦ: Ag) level by a sandwich enzyme-linked immunoabsorbsent assay. All exons, exon-intron boundaries and 3', 5'untranslated regions of the FⅦ gene from the genomic DNA of the probands and their families were amplified by PCR, and then sequenced. Results PT was significantly prolonged, and FⅦ: C and FⅦ: Ag were decreased and the following mutations were identified in the four probands: a homozygous transversion of 18041 T→G resulting in His408→Gln substitution in exon 8 in proband 1, a homozygous double nucleotide deletion, del CT (5078-5079) in exon 1 in proband 2, a double heterozygous of IVS6-1G→A and Gln426→stop in proband 3, and a double heterozygous of IVS6-1G→A and Arg364Gln in prohand 4. Conclusion Two missense mutations, His408Gln, Arg364Gln and one nonsense,Gln426stop in the catalytic domain of FⅦ and one double nucleotide deletion, del CT(5078-5079) in exon 1 and one splicesome mutation, IVS6-1G→A in intron 6 were separately identified in four Chinese pedigrees with inherited coagulation factor Ⅶ deficiency. The Gln426stop and IVS6-1G→A were first identified in the world and the homozygous del CT(5078-5079) and His408Gln were first found in China.