女性血友病A FⅧ基因的双重杂合突变-1例基因分析  

Double Heterozygote Mutations of F8 gene in Female with Hemophilia A-Gene Analysis for 1 Case

作　　者：蔡晓红[1] 王学锋[1] 方怡[1] 戴菁[1] 丁秋兰[1] 王文斌[1] 谢爽[1] 谢飞[1] 王鸿利[1] 

机构地区：[1]上海第二医科大学附属瑞金医院临床输血科 上海血液学研究所,上海200025

出　　处：《血栓与止血学》2005年第2期52-56,共5页Chinese Journal of Thrombosis and Hemostasis

摘　　要：目的对1例女性血友病A(HA)患者家系进行基因分析,以探讨其分子发病机制。方法FⅧ:C等测定进行HA表型诊断;用LD-PCR进行内含子22倒位检测,对FⅧ基因的所有外显子及其侧翼序列进行扩增,用末端标记双脱氧法检测核酸序列。结果表型检测先证者(父亲)及其女儿的FⅧ:C分别为6.9%、3.4%;3人内含子22倒位为阴性;先证者女儿FⅧ14号外显子存在自发杂合突变(112183-112191)insA,18号外显子131252T→C(Leu1975Pro); 父亲FⅧ18号外显子存在相同突变,母亲FⅧ基因检测没有发现先证者的这2个突变。结论FⅧ14号外显子(112183-112191)insA与18号外显子131252T→C双重杂合突变可能是导致该患者HA的分子机制,其中18号外显子131252T→C为国际首次报道,14号外显子(112183-112191)insA为国内首次报道。Objective To identify the mutations of coagulation factor Ⅷ in a female with hemophilia A. Methods The plasma FⅧ :C et al was determined used the peripheral blood samples. Intron 22 inversion was excluded by LD-PCR,then all the exons and exon-intron boundaries of factor Ⅷ gene were analyzed by PCR and direct DNA sequencing. Results FⅧ:C of the proband and his daughter were 6. 9% and 3. 4% , respectively, each of them three had no intron 22 inversion. Double heterozygote mutation were detected in the female;a spontaneous heterozygous A insertion in a sequence of 9 As ( codons 1191-1194) within exon 14, and a heterozygous missense mutation in exon 18 (131252T→C) resulting in Leu1975Pro,which was the only mutation in all the exons and exon-intron boundaries in the proband. Proband' s wife had no mutations in these 2 site. Conclusion The FⅧ deficiency of the female are propably caused by the framshift of (112183-112191)insA and the missense mutation of 131252T→C which is a novel mutation in F8 gene.

关 键 词：血友病A 女性患者 因子Ⅷ 突变 核酸测序 

分 类 号：R554[医药卫生—血液循环系统疾病]