Background

Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene (SERPING1) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients.

Methods

Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations in SERPING1 were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger.

Results

Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T˃C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA.

Conclusion

Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4.

中文翻译：

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I 型和 II 型遗传性血管性水肿的遗传学研究（伊朗患者的第一份报告：描述三种新突变）。

背景

遗传性血管性水肿 (HAE) 是一种罕见的常染色体显性免疫缺陷病，其 C1 抑制基因 ( SERPING1 ) 突变导致 C1-INH 蛋白的缺陷和功能障碍分别导致 HAE I 型或 II 型。本研究旨在确定伊朗患者中 HAE I 型和 II 型的遗传谱。

方法

34 名临床表型为面部、上下肢、手部和上呼吸道反复水肿发作的患者进入了研究。使用 PCR 和 Sanger 测序分析SERPING1中的突变。此外，Sanger 进行了多重连接依赖性探针扩增 (MLPA) 以发现阴性筛选样品中的大缺失或重复。

结果

23 名患者被诊断为 HAE I 型，11 名患者被诊断为 HAE II 型。十四种独特的致病变异，包括五种移码（p.G217Vfs*、p.V454Gfs*18、p.S422Lfs*9、p.S36Ffs*21、p.L243Cfs*9），七种错义变异（p.A2V、p.G493R、p .V147E、p.G143R、p.L481P、p.P399H、p.R466C)、一种无意义的 (p.R494*) 和一种剪接缺陷 (C.51 + 2 T˃C)，其中三个突变是鉴定小说。然而，通过 Sanger 测序和 MLPA 在 7 名患者中未发现突变。

结论

在对 C1INH 水平和功能进行临床评估和评估后，通过 HAE 的突变分析进行最终诊断可以预防该疾病的潜在风险和危及生命的表现。此外，基因诊断在促进早期诊断、症状前诊断、儿童早期诊断、无症状病例以及那些具有C1-INH缺乏和/或C4临界生化结果的患者方面发挥重要作用。