Frequent life-threatening laryngeal attacks in two Croatian families with hereditary angioedema due to C1 inhibitor deficiency harbouring a novel frameshift mutation in SERPING1

• Published in: Annals of medicine (Helsinki) Vol. 48; no. 7; p. 485
• Main Authors: Karadža-Lapić, Ljerka, Korošec, Peter, Šilar, Mira, Košnik, Mitja, Cikojević, Draško, Lozić, Bernarda, Rijavec, Matija
• Format: Journal Article
• Language: English
• Published: England 02.10.2016
• Subjects: Adolescent; Adult; Aged; Angioedemas, Hereditary - genetics; Child, Preschool; Complement C1 Inactivator Proteins - deficiency; Complement C1 Inactivator Proteins - genetics; Complement C1 Inhibitor Protein; Croatia; Female; Frameshift Mutation; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Pedigree; Young Adult; hereditary angioedema; Attacks; laryngeal oedema; frameshift SERPING1 mutation
• ISSN: 1365-2060
• DOI: 10.1080/07853890.2016.1185144

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. Twenty-three subjects from two families were recruited for clinical data evaluation and molecular analysis at General Hospital Šibenik, Croatia. 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. 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.