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.
Keywords: Attacks; frameshift SERPING1 mutation; hereditary angioedema; laryngeal oedema.