Frequent life-threatening laryngeal attacks in two Croatian families with hereditary angioedema due to C1 inhibitor deficiency harbouring a novel frameshift mutation in SERPING1. (2nd October 2016)

• Record Type: Journal Article
• Authors: Karadža-Lapić, Ljerka; Korošec, Peter; Šilar, Mira; Košnik, Mitja; Cikojević, Draško; Lozić, Bernarda; Rijavec, Matija
• Is Part Of: Annals of medicine. Volume 48:Number 7(2016)
• Page Start: 485
• Page End: 491
• Publication Date: 2016-10-02
• Subjects: Attacks -- frameshift SERPING1 mutation -- hereditary angioedema -- laryngeal oedema; Medicine -- Periodicals; 610
• DOI: 10.1080/07853890.2016.1185144
• Languages: English
• ISSNs: 0785-3890

Abstract

Abstract: Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease caused by mutations in the SERPING1 gene. It can affect many regions in the body, but potentially life-threatening laryngeal oedemas are of concern. Methods: Twenty-three subjects from two families were recruited for clinical data evaluation and molecular analysis at General Hospital Šibenik, Croatia. Results: Decreased levels of C1 inhibitor were detected in 12 adult patients and three young asymptomatic persons. The same novel deletion of two nucleotides on exon 3 (c.74_75delAT) was identified in all of them. A history of laryngeal oedema was present in 10 patients (83%), and all patients reported laryngeal attacks at least once a year. The delay in diagnosis decreased noticeably from the first to the last generation. Conclusions: We identified a novel causative mutation in SERPING1 in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype–phenotype relationship. Key messages: Hereditary angioedema due to C1 inhibitor deficiency is a rare autosomal dominant disease caused by mutations in the SERPING1 gene, and laryngeal oedema is of concern because it can cause death by asphyxiation. A novel causative mutation in SERPING1, a deletion of two nucleotides on exon 3 (c.74_75delAT), was identified in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype–phenotype relationship because it appears that the mutation type may affect disease severity.