Mutations in C1-INH-defiency

Principal investigator(s):


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, treatment 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 SERPING1 mutations in Norwegian patients with C1-INH-HAE are largely undescribed and could help in diagnosis, 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 suspected 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 eight (15.4%) suffered from C1-INH-HAE type II. Pathogenic or likely pathogenic mutations were found in 22/25 families (88%). Thirteen unique mutations were detected, including six previously undescribed. There were three missense mutations including one mutation affecting the reactive center loop at codon 466, three nonsense mutations, three small deletions/duplications, three gross deletions, and one splice mutation. Read More

We discovered a deep intronic mutation: c.1029 + 384A > G, in intron 6 which is responsible for HAE type I  in a large norwegian family in 2017, but have not yet published it.

The same mutation was published in 2020 by a group from the Czech Republic.