Freiberger Tomás, Kolárová Lenka, Mejstrík Pavel, Vyskocilová Martina, Kuklínek Pavel, Litzman Jirí
Department of Immunogenetics, Research Institute of Child Health, Brno, Czech Republic.
Hum Mutat. 2002 Apr;19(4):461. doi: 10.1002/humu.9029.
Hereditary angioedema (HAE) is a disorder characterised by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 inh, or C1NH). Most patients with HAE have an absolute deficiency of C1 inh (type I HAE) while the rest (15% of kindreds) synthetize a dysfunctional C1 inh protein (type II HAE). In this report a novel use of denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing of the C1 inhibitor gene is presented. Five novel mutations, one nonsense (p.S48X) and four small deletions resulting in frameshifts (g.2264-2265delAG, g.2304delC, g.8493-8494delCC and g.16676-16677delTG) have been identified in the C1 inhibitor gene in five families with type I HAE. All of these mutations lead to premature termination of translation and thus can be considered causative of the C1 inh deficiency. Moreover, two previously described mutations in the reactive center of C1 inh, p.R444C and p.R444H, have been detected in four unrelated patients with type II HAE.
遗传性血管性水肿（HAE）是一种以局部皮下或粘膜下水肿反复发作发作为特征的疾病。它以常染色体显性方式遗传，由C1抑制因子（C1 inh，或C1NH）缺乏引起。大多数HAE患者存在C1 inh绝对缺乏（I型HAE），而其余患者（15%的家族）合成功能失调的C1 inh蛋白（II型HAE）。在本报告中，介绍了变性梯度凝胶电泳（DGGE）继以C1抑制因子基因直接测序的一种新用途。在五个I型HAE家族的C1抑制因子基因中鉴定出五个新突变，一个无义突变（p.S48X）和四个导致移码的小缺失（g.2264 - 2265delAG、g.2304delC、g.8493 - 8494delCC和g.16676 - 16677delTG）。所有这些突变均导致翻译提前终止，因此可被视为C1 inh缺乏的病因。此外，在四名无关的II型HAE患者中检测到C1 inh反应中心两个先前描述的突变，p.R444C和p.R444H。
