遗传性出血性毛细血管扩张症致严重鼻出血的早期基因诊断

Early genetic diagnosis in patients with HHT induced severe nosebleed

目的:探讨遗传性出血性毛细血管扩张症(HHT)致严重鼻出血的早期基因诊断。方法:对2个HHT家系共23例成员进行详细的临床检查及评估,提取外周静脉血DNA,聚合酶链反应扩增目的基因ENG和ACVRL-1,测序并进行序列分析,判断突变的致病性。结果:NMG-1家系采集到静脉血标本的11例中有6例携带ACVRL-1基因的错义突变c.263A>G。GD-2家系采集到静脉血标本的12例中有5例携带ACVRL-1基因的错义突变c.199C>G。有鼻出血病史者突变基因检出率为100%,无鼻出血者史突变基因检出率为25%。结论:基因诊断极高的灵敏度和特异性在HHT早期诊断中具有重要的应用价值,可成为临床常规检测项目。

Objective：To study the early gene diagnosis of hereditary hemorrhagic telangiectasia（HHT） in- duced severe nosebleed. Method：Clinical features of 23 family members in two H HT pedigrees were examined. Ge- nomic DNA was extracted from peripheral blood samples. PCR amplification was conducted to screen ENG and ACVRL-1 genes with their specific primers. Direct sequencing was performed to detect the mutation. Mutation a- nalysis was carried out to evaluate its significance. Result： A heterozygous c. 263A〉G mutation was identified in exon 3 of ACVRL-1 in 6 out of 11 members in NMG-1 pedigree. In GD-2 pedigree, 5 of 11 members carried c. 199C〉G mutation. Mutation detection rate was 100 % in subjects with nosebleed history and 25 % in family mem- bers without epistaxis. Conclusion：Gene diagnosis characterized by high sensitivity and specificity is of great practi- cal significance and early genetic screening should be a clinical routine test for HHT induced severe nosebleed.