西北地区血友病B患者FⅨ基因突变的分析

Analysis for the mutation of FⅨ gene in patients with Hemophilia B in nothwest China

目的:为了研究中国西北地区血友病B(HB)患者的FⅨ基因的突变谱的特征,建立最优化的分子诊断策略和找出基因型-表型的相互关系。方法:受试者包括3个中国西北地区无亲缘关系的血友病B患者,APTT和FⅨ:C用来进行表型诊断;利用聚合酶链反应(PCR)扩增和直接测序F9基因的全部外显子和侧翼序列。结果:总共有3个不同的突变被检测到,(突变检测率达到了100%)1号患者有外显子2点突变(A→C);2号患者有外显子8点突变(G→A);3号有外显子2点突变(C/T型)。结论:通过对3名中国西部地区血友病B患者的结果分析显示,其没有突变热点;直接测序所有的外显子和侧翼序列被认为是血友病B患者诊断的金标准;突变类型和基因缺失的严重程度的基因型-表型的相关性并不一致。

Objective：To characterize the mutation spectrum of F9 in the northwest of China patients with HB to establish the optimal molecular diagnostic strategy and to find genotype-phenotype correlations.Methods： Study subjects consisted of 3 unrelated patients of Northwest of china with HB.The activated partial thrombop lastin time（APTT） and FIX activity（FⅨ：C） tests were adopted for phenotype diagnosis;Polymerase chain reaction（PCR）amplification and direct sequencing of all exons and flanking sequences of F9 were performed.Results： A total of 3 unique mutations were detected,（mutation detection rate100%）,the point mutation of exon 2 was found in patient No 1（A→C）;the point mutation of exon8 existed in patient No 2（G→A）;the point mutation of exon2 was detected in patient No 3（C/T）.Conclusion： Based on our results from 3 Northwest of china patients with HB,which showed no hotspot for mutations,direct sequencing of all exons with flanking sequences is as the golden standard for HB patient.The genotype-phenotype correlations between the type of mutation and the severity of factor deficiency were not consistent.