论文部分内容阅读
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 investigate the molecular pathogenesis of a pedigree of female hemophilia A (HA) patients. Methods F Ⅷ: C and other assays for the diagnosis of HA phenotype; LD-PCR intron 22 inverted detection of all the FⅧ gene exons and flanking sequences were amplified by end-labeling dideoxy method to detect the nucleic acid sequence . Results FⅧ: C of phenotypic test proband (father) and his daughter were 6.9% and 3.4%, respectively. Infertility mutation of 3 intron 22 was negative. 112183-112191) insA, exon 18 of 131252T → C (Leu1975Pro); the same mutation was found in the exon of FⅧ18 in the father, and no mutation was found in the FⅧ gene of the mother. Conclusion The double mutation of insular FⅧ14 exon (112183-112191) and exon 18 131252T → C may be the molecular mechanism of HA in this patient. Exon 18 of 13182T → C is the first reported in the world and exon 14 (112183-112191) insA is the first report in China.