Detection of C1 inhibitor mutations in patients with hereditary angioedema

J Allergy Clin Immunol. 2000 Mar;105(3):541-6. doi: 10.1067/mai.2000.104780.


Background: Hereditary angioedema (HAE) results from a deficiency in the functional level of C1 inhibitor caused by mutations in the C1 inhibitor gene. The mutations responsible for HAE have been shown to be heterogeneous.

Objective: Because the identification of C1 inhibitor mutations may depend, in part, on the technique used to screen for mutations, we screened the entire C1 inhibitor coding region to identify mutations in a cohort of patients with HAE.

Methods: By using single-stranded conformational polymorphism analysis, 24 subjects with HAE from 16 different kindreds were screened for C1 inhibitor polymorphisms. C1 inhibitor mutations were identified by sequencing the exons containing identified polymorphisms.

Results: All 24 subjects with HAE had identifiable polymorphisms, involving exons 2, 3, 4, 5, or 8. Fourteen different C1 inhibitor mutations were identified: 8 missense, 1 nonsense, 4 frameshift, and 1 small deletion mutations. No large deletions or duplications were found. Nine of the 14 mutations represent newly recognized C1 inhibitor mutations, 6 of which involve exon 4.

Conclusions: Single-stranded conformational polymorphism is an effective approach for identifying new mutations in HAE. Elucidation of the range of C1 inhibitor mutations causing HAE is important for both defining which residues are required for C1 inhibitor secretion or function and providing the basis for future studies to define the relationship between the C1 inhibitor genotype and disease severity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angioedema / genetics*
  • Base Sequence
  • Complement C1 Inactivator Proteins / genetics*
  • DNA Primers
  • Family Health
  • Frameshift Mutation
  • Gene Deletion
  • Humans
  • Mutation
  • Mutation, Missense
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational


  • Complement C1 Inactivator Proteins
  • DNA Primers