83 Hereditary Angioedema and Normal C1-Inhibitor (HAE TYPE III): A Novel Mutation in the Coagulation Factor 12 Gene

BACKGROUND: Hereditary angioedema with normal C1-inhibitor and mutations in the coagulation factor 12 gene is a recently described disease entity that occurs predominantly in women. Up to date, 2 different missense mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported, co-segregating with clinical signs. Aim of the study was to assess the clinical symptoms, mutations in the factor 12 gene, and plasma parameters of this disease in a family with hereditary angioedema with normal C1-inhibitor. METHODS: Six members of one family were studied, including 2 women with recurrent angioedema. Mutation analysis of the factor XII gene was performed. RESULTS: By sequencing the factor 12 gene, a hitherto unknown mutation, the deletion of 72 base pairs (c.971_1018+24del72*), was identified in a family of Turkish origin, in 2 women with recurrent skin swellings and abdominal pain attacks, and in their symptom-free father. The novel mutation c.971_1018+24del72* caused a loss of 48 base pairs of exon 9 (coding amino acids 324* to 340*) in addition to 24 base pairs of intron 9, including the authentic donor splice site of exon 9. All carriers of this mutation had normal plasma concentrations and activity of C1-inhibitor, C4, factor XII clotting activity, and activated partial thromboplastin times. CONCLUSIONS: The novel deletion mutation in the factor 12 gene was located in the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg* reported previously, suggesting the importance of the exon 9 to intron 9 DNA region for the development of hereditary angioedema with normal C1-inhibitor.