On the basis of co-segregation patterns, two different missense mutations in 6 index patients of 20 families (confirmed in 22 additional family members), mapping to 5 q 33-qter of F12 (Online Mendelian Inheritance in Man, [OMIM] 610619) were identified in European pedigrees of hereditary angioedema with normal C1-INH. The gene discussed is SERPING1; the disease is hereditary angioedema.