三个血友病B家系的基因诊断

Gene diagnosis of 3 haemophilia B families

目的探讨中国汉族3个无关血友病B家系先证者凝血因子Ⅸ（FⅨ）基因突变及分子发病机制，对家系女性成员进行携带者诊断。方法家系先证者及成员采静脉血，先证者表型诊断确诊后，检测先证者及其家系成员6个STR位点的基因多态性，进行家系遗传连锁分析，应用PCR法对先证者及可疑携带者FⅨ8个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。结果家系1先证者FⅨ基因外显子6发现G22119A突变，家系2先证者FⅨ基因外显子2发现G7392C突变，家系3先证者FⅨ基因外显子8发现T32685C突变。结论血友病B先证者FⅨ基因缺陷是其发病的分子机制。

Objective To explore factor Ⅸ gene mutations and molecular mechanism of haemophilia B in 3 unrelated families. Methods The activated partial thromboplastin time （APTT） and FⅨ activity （ FⅨ： C） assay were used for phenotypic diagnosis. The STR loci gene polymorphisms for genetic linkage analysis in the patients and their family members were assayed. All of the 8 exons and the exon-intron boundaries of FⅨ gene were amplified by polymerase chain reaction （PCR） and direct sequencing. Results and Conclusion Mutations were found in the FIX gene of the propositi. Proband 1 had a G22119A mutation in exon 6, proband 2 a G7392C mutation in exon 2 and proband 3 a T32685C mutation in exon 8.