Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is caused by mutations affecting the SERPING1 gene. Adult patients (≥ 18 years old) diagnosed with C1-INH-HAE were clustered according to a modified SERPING1 gene mutation classification [5]. Demographic, clinical, and laboratory data were studied. Published manuscripts on the genotype/phenotype relationship were reviewed. Eighty-eight patients participated in the study, with 78 having a classifiable mutation. We compared the data in the 3 largest groups: class 0 only (n = 32), class II only (n = 18), class III only (n = 22). Antigenic C4 and C1 inhibitors were higher in class II (p = 0.008 and p = 0.02, respectively), and facial attacks in the last 6 months were more frequent in class III (p = 0.04)). All the other differences were non-significant. Twelve manuscripts on phenotype/genotype correlation were found: missense mutations in SERPING1 gene were associated with delay in disease onset and lower severity score in some studies, whereas the CC F12-C46T/C polymorphism produced earlier disease onset. Our study shows minimal differences regarding clinical phenotype in patients with class 0, II, and III SERPING1 gene mutations, with a tendency to class III having a more severe phenotype. The study should be performed in a larger sample to confirm if they are significant.

We propose that larger multicenter, international studies are performed, comparing different SERPING1 gene mutation classifications, combining polymorphisms in other involved genes (kallikrein-kinin system, regulation of vasculature, plasminogen activation) and using different variables and clinical scores to assess C1-INH-HAE disease activity and/or severity in order to study possible genotype/phenotype relationships.

由于 C1 抑制剂缺乏症 (C1-INH-HAE) 导致的遗传性血管性水肿是由影响 SERPING1 基因的突变引起的。诊断为 C1-INH-HAE 的成年患者（≥ 18 岁）根据修改后的 SERPING1 基因突变分类进行聚类 [5]。研究了人口统计学、临床和实验室数据。已发表的关于基因型/表型关系的手稿进行了审查。88 名患者参与了这项研究，其中 78 名具有可分类的突变。我们比较了 3 个最大组的数据：仅 0 类 ( n  = 32)、仅 II 类 ( n  = 18)、仅 III 类 ( n  = 22)。抗原性 C4 和 C1 抑制剂在 II 类中较高（p  = 0.008 和p = 0.02，分别），并且过去 6 个月的面部攻击在 III 类中更频繁（p  = 0.04））。所有其他差异均不显着。发现了 12 篇关于表型/基因型相关性的手稿：在一些研究中，SERPING1 基因的错义突变与疾病发作的延迟和严重程度评分的降低有关，而 CC F12-C46T/C 多态性导致疾病的早期发作。我们的研究显示，具有 0、II 和 III 类 SERPING1 基因突变的患者的临床表型差异很小，而 III 类具有更严重的表型。该研究应该在更大的样本中进行，以确认它们是否显着。

我们建议进行更大规模的多中心国际研究，比较不同的 SERPING1 基因突变分类，结合其他相关基因的多态性（激肽释放酶-激肽系统、脉管系统调节、纤溶酶原激活）并使用不同的变量和临床评分来评估 C1-INH- HAE 疾病活动和/或严重程度，以研究可能的基因型/表型关系。