Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Clinical and Molecular Genetic Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Research Unit in Translational Bioinformatics in Neurosciences, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Clin Immunol. 2014 Feb;150(2):143-8. doi: 10.1016/j.clim.2013.11.013. Epub 2013 Dec 4.
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal-dominant disease caused by mutations in SERPING1 gene. The main clinical feature of C1INH deficiency is the spontaneous edema of the subcutaneous and submucosal layers. More than 280 different mutations scattering the entire SERPING1 gene have been reported. We identified and characterized a new mutation in SERPING1 gene in a Spanish family with hereditary angioedema. The mutation (c.685 + 2 T > A) disrupts the donor splice site of intron 4 leading to the loss of exon 4 in mutant mRNA. We demonstrated that mutant mRNA is mostly degraded, probably by the surveillance pathway no-go mRNA decay. Bioinformatic analysis showed that the mutant protein, if produced, would be non-functional since the protein lacks a stretch of 45 amino acids affecting the functional RCL loop. Finally, we found a reduction of the wild-type mRNA expression in c.685 + 2 T > A carriers.
由于 C1 抑制剂缺乏引起的遗传性血管水肿（HAE-C1INH）是一种罕见的常染色体显性遗传疾病，由 SERPING1 基因突变引起。C1INH 缺乏的主要临床特征是皮下和粘膜下层的自发性水肿。已经报道了超过 280 种不同的突变，分布在整个 SERPING1 基因中。我们在一个西班牙遗传性血管水肿家族中鉴定并表征了 SERPING1 基因的一个新突变。该突变（c.685+2T＞A）破坏了内含子 4 的供体位点，导致突变 mRNA 中缺失外显子 4。我们证明，突变 mRNA 主要被降解，可能是通过监控途径非编码 mRNA 衰减。生物信息学分析表明，如果产生突变蛋白，由于该蛋白缺失一段 45 个氨基酸的功能 RCL 环，因此是无功能的。最后，我们发现 c.685+2T＞A 携带者中野生型 mRNA 表达减少。
