遗传性血管水肿（HAE）临床异质性的分子机制

项目名称： 遗传性血管水肿（HAE）临床异质性的分子机制

项目编号： No.81472870

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 支玉香

作者单位： 中国医学科学院北京协和医院

项目金额： 70万元

中文摘要： 遗传性血管性水肿（hereditary angioedema, HAE）是一种少见的常染色体显性遗传病，30-40%患者因发生喉水肿而严重威胁病人的生命。HAE发病机制主要是补体C1抑制物(C1 inhibitor, C1 INH)基因突变导致C1-INH表达量减少或功能缺陷。我们前期已收集到300余例病人，对部分患者进行了C1-INH基因突变及临床特点分析，结果发现此病具有明显的临床异质性，甚至携带相同突变的同一家系不同成员间的症状严重度相差甚远，但导致这一异质性的遗传改变尚不清楚；此外有部分患者未在C1-INH基因上发现致病突变。为此，我们拟（1）完善家系调查，对未发现致病突变的患者进一步寻找新的突变位点或潜在的新的致病基因，建立基因突变谱；（2）探索不同突变类型与临床表现之间的相关性，并探寻可能影响HAE严重程度的复合杂合性突变或修饰基因，作为评估病情及预后的检测指标。

中文关键词： 遗传性血管水肿；临床异质性；C1；抑制物；基因突变

英文摘要： Hereditary angioedema (HAE) is a rare autosomal dominant disease，caused by a deficiency of C1 inhibitor (C1-INH). HAE is life-threatening disease because 30-40% of patients with upper airway angioedema died from asphyxiation. HAE presents as remarkable heterogeneity in manifestations, even in the same family. In the previous studies, we have collected more than 300 patients, identified mutations in C1-INH gene and analyzed the clinical features in part of them. The results showed that the manifestations of HAE are various, and even in the same family, the severity of involved members is quite different. The present program aims to: (1) complete family survey and determine novel mutation of C1-INH gene or new causative gene in the patients failing to identify mutations by PCR; (2) statistically analyze the potential correlation between mutational types of C1-INH gene and the manifestation of HAE, and try to explore the mixed heterozygous mutation or modifier gene which may affect the severity of HAE and provide molecular biological evidence for the clinical heterogeneity of HAE.

英文关键词： hereditary angioedema;clinical heterogeneity;C1 inhibitor;gene mutatioan