Dewald Georg, Bork Konrad
Institut d'Immunologie et d'Hématologie, Faculté de médecine, Université Louis Pasteur, 4 rue Kirschleger, 67085 Strasbourg Cedex, France.
Biochem Biophys Res Commun. 2006 May 19;343(4):1286-9. doi: 10.1016/j.bbrc.2006.03.092.
Hereditary angioedema is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types are both caused by mutations within the complement C1 inhibitor gene. A recently described new type does not show a deficiency of C1 inhibitor and affects almost exclusively women. We screened twenty unrelated index patients with this new type of hereditary angioedema for mutations in the coagulation factor XII gene. Two different missense mutations were identified in exactly the same position within exon 9 of the F12 gene. 'Mutation 1' (1032C-->A), encountered in five patients, predicts a threonine-to-lysine substitution (Thr309Lys). 'Mutation 2' (1032C-->G), observed in one patient, results in a threonine-to-arginine substitution (Thr309Arg). The predicted structural and functional impact of the mutations, their absence in 145 healthy controls, and their co-segregation with the phenotype in five families provide strong support that they cause disease.
遗传性血管性水肿的特征为反复出现皮肤肿胀、腹痛发作，以及可能危及生命的上呼吸道梗阻。两种经典类型均由补体C1抑制因子基因突变所致。最近描述的一种新型并非由C1抑制因子缺乏引起，且几乎仅影响女性。我们对20例患有这种新型遗传性血管性水肿的无关索引患者进行筛查，以寻找凝血因子XII基因中的突变。在F12基因第9外显子的完全相同位置鉴定出两种不同的错义突变。在5例患者中发现的“突变1”（1032C→A）预测会发生苏氨酸到赖氨酸的替换（Thr309Lys）。在1例患者中观察到的“突变2”（1032C→G）导致苏氨酸到精氨酸的替换（Thr309Arg）。这些突变对结构和功能的预测影响、在145名健康对照中的未出现，以及在5个家族中与表型的共分离，有力支持了它们会导致疾病这一观点。
