C1抑制物基因突变提前形成终止密码子导致遗传性血管水肿

Hereditary Angioedema Resulting from C1 Inhibitor Gene Mutation Leading to Premature Stop Codons

目的检测7例来自不同遗传性血管水肿家系患者进行C1抑制物(C1 inhibitor,C1INH)基因突变。方法 2011至2012年北京协和医院变态反应科诊断为Ⅰ型HAE的7例来自不同HAE家系的先证者及53名健康成人为研究对象,采集外周静脉血,提取基因组DNA,聚合酶链反应扩增C1 INH基因的8个外显子及其相邻序列并进行序列检测。将检测结果与GenBank公布的C1INH基因序列相比较,确定突变及基因多态性。结果 7例患者C1INH基因序列中均鉴定到致病突变,分别为c.289 C<T、c.538 C<T、c.794 G<A、c.44 delT、c.939 delT、c.1214-1223 delCCAGCCAGGA及c.1279 delC。包括3种无义突变及4种移码突变,其中5种为首次报道。以上7种突变均通过提前形成终止密码子导致C1INH表达缺陷,且于53名健康成人中均未见上述改变。检测到的7种单核苷酸多态性分别为g.1965G>A,g.3248T>C,g.3493T>C,g.5755G>A,g.9498T>C,g.15193A>G,g.18012G>A。结论本研究鉴定的7种不同C1INH基因突变中有5种为国内外首次报道,丰富了中国C1INH基因突变数据库。

Objective To detect C1 inhibitor gene mutations in 7 HAE patients from different families. Methods Seven HAE patients with from different families and 53 healthy controls were recruited in this study. Peripheral blood was collected for genome DNA extraction. All the eight exons and intron-exon boundaries of C1 inhibitor gene were amplified by PCR and sequenced. Mutations and SNPs were detected by alignment with the reference sequences from GenBank. Results Mutations were identified in all the 7 patients ： c. 289 C 〈 T, c. 538 C 〈 T, c. 794 G 〈 A, c. 44 delT, c. 939 delT, c. 1214-1223 delCCAGCCAGGA and c. 1279 delC. All the mutation formed a premature stop codon which resulted in deficient expression of CI-INH. All the mutations were not shown in the controls. 7 SNPs were discovered in this patient group （ g. 1965 G 〉 A, g. 3248T〉C, g. 3493T 〉 C, g. 5755 G 〉 A, g. 9498 T 〉 C, g. 15193 A 〉 G, g. 18012 G 〉 A）. Conclusions Totally 7 different mutations of CI-INH gene （3 nonsense and 4 frame shift） were detected in 7 HAE patients, 5 of them were reported for the first time. 7 SNPs were also identified in this patient group.