RESEARCH ARTICLE A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1

Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by relapsing, non-pruritic swelling in skin and submucosal tissue. Symptoms can appear in early infancy when diagnosis is more difficult. In the absence of a correct diagnosis, treat-ment of abdominal attacks often lead to unnecessary surgery, and laryngeal edema can cause asphyxiation. A cohort study of 52 patients from 25 unrelated families in Norway was studied. Diagnosis of C1-INH-HAE was based on international consensus criteria including low functional and/or antigenic C1-INH values and antigenic C4. As SERPING1mutations in Norwegian patients with C1-INH-HAE are largely undescribed and could help in diagno-sis, we aimed to find and describe these mutations. Mutation analysis of the SERPING1 gene was performed by Sanger sequencing of all protein coding exons and exon-intron boundaries. Samples without detected mutation were further analyzed by multiplex ligation-dependent probe amplification to detect deletions and duplications. Novel mutations sus-pected to lead to splice defects were analyzed on the mRNA level. Fifty-two patients from 25 families were included. Forty-four (84,6%) suffered from C1-INH-HAE type I and eigh