ArticleThe Journal of allergy and clinical immunology2023
Insights into the pathogenesis of hereditary angioedema using genetic sequencing and recombinant protein expression analyses.
Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Beyond the Index Case: A Practical Framework for Cascade Family Screening in Hereditary Angioedema.Clinical reviews in allergy & immunology · 2026Review
- Characterization of missense variants in the signal peptide of C1 esterase inhibitor.The Journal of allergy and clinical immunology · 2026Article
- Beyond Swelling: Clinical Insights into the Diagnosis and Management of Hereditary Angioedema.International journal of molecular sciences · 2026Review
- Family Tree Mapping of Genetic and Phenotypic Codes of Hereditary Angioedema.Medicina (Kaunas, Lithuania) · 2026Article
- Article
- A novel SERPING1 splice-site variant (c.1029 + 2T > A) causing hereditary angioedema type I: functional characterization and clinical analysis.Orphanet journal of rare diseases · 2026Article
- The 2025 WAO Guidelines for the classification, diagnosis, and treatment of hereditary angioedema, with consideration of worldwide disparities.The World Allergy Organization journal · 2026Article
- Epidemiological and clinical characteristics of hereditary angioedema in the Baltic states.Frontiers in immunology · 2026Article
- Therapeutic Advances in Hereditary Angioedema: A Focus on Present and Future Options.Advances in therapy · 2025Review
- Utility of in Vivo and Ex-vivo Models in Food Allergy Research: Lessons for Shrimp Allergy.Clinical reviews in allergy & immunology · 2025Review
- Hereditary angioedema diagnosis: Reflecting on the past, envisioning the future.The World Allergy Organization journal · 2025Review
- Integrative transcriptomic and proteomic analysis reveals that SERPING1 inhibits neuronal proliferationWorld journal of psychiatry · 2025Article
- N-glycosylation in the SERPIN domain of the C1-esterase inhibitor in hereditary angioedema.JCI insight · 2025Article
- Uncovering a novel SERPING1 pathogenic variant: insights into the aggregation of C1-INH in hereditary angioedema.Orphanet journal of rare diseases · 2024Article
- Hereditary or acquired? Comprehensive genetic testing assists in stratifying angioedema patients.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2024Article
- RecessiveJournal of clinical medicine · 2023Article
- Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort.Journal of clinical immunology · 2023Article
- Complementing Testicular Immune Regulation: The Relationship between Sertoli Cells, Complement, and the Immune Response.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe pathogenesis of hereditary angioedema (HAE) type I and type II is linked to defective C1 esterase inhibitor (C1-INH) encoded by the SERPING1 gene. There are substantial variabilities in the clinical presentations of patients with HAE that are not directly correlated to the serum levels of C1-INH. The impact of SERPING1 variants on C1-INH expression, structure, and function is incompletely understood.
objectiveTo investigate the influence of SERPING1 variants on the C1-INH expression, structure, and function of 20 patients with HAE from 14 families with no prior genetic diagnosis.
methodsPatients underwent whole-exome sequencing (WES). If no variants were identified, whole-genome sequencing (WGS) was performed. Except for the frameshift and large deletions, each C1-INH variant was recombinantly produced and, if synthesized and secreted, was subjected to structural, oligosaccharide, and functional analyses.
resultsWe identified 11 heterozygous variants in the SERPING1 gene, of which 5 were classified as pathogenic (E85Dfs∗63, N166Qfs∗91, K201Qfs∗56, P399A, and R466H) and 6 as variants of uncertain significance (C130W, I224S, N272del, K273del, L349F, and F471C). Three large heterozygous deletions were discovered through WGS. Our data indicate that C130W, N272del, P399A, and F471C are poorly synthesized, I224S prevents proper C1-INH folding, and K273del impairs C1-INH function by adding an additional oligosaccharide. Further evaluation suggests that compound variant P399A/L349F contributes to a more severe clinical phenotype.
conclusionsOur combined approach of WES and WGS uncovered SERPING1 gene alternations in each patient. The recombinant protein production followed by systematic antigenic, structural, and functional assessment facilitates the identification of underlying pathogenic mechanisms in HAE.
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