title: A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1.
abstract: 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.
authors.affiliation: Department of Dermatology, Oslo University Hospital, Rikshospitalet, N 0027, Oslo, Norway.
authors.forename: Irene
authors.initials: I
authors.lastname: Johnsrud
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, N 0027, Oslo, Norway.
authors.forename: Mari Ann
authors.initials: MA
authors.lastname: Kulseth
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, N 0027, Oslo, Norway.
authors.forename: Olaug Kristin
authors.initials: OK
authors.lastname: Rødningen
authors.affiliation: Department of Dermatology, Oslo University Hospital, Rikshospitalet, N 0027, Oslo, Norway.
authors.forename: Linn
authors.initials: L
authors.lastname: Landrø
authors.affiliation: Department of Dermatology, Oslo University Hospital, Rikshospitalet, N 0027, Oslo, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Helsing
authors.affiliation: Department of Anesthesiology, Nordland Hospital, N 8092, Bodø, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Waage Nielsen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, N 0027, Oslo, Norway.
authors.forename: Ketil
authors.initials: K
authors.lastname: Heimdal
mesh_terms: D054179:Angioedemas, Hereditary / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation / Q000235:genetics*; D009664:Norway
chemical_list: D050718:Complement C1 Inhibitor Protein