title: First case of homozygous C1 inhibitor deficiency.
abstract: BACKGROUND
  C1 Inhibitor (C1-Inh) deficiency causes angioedema and can be hereditary (HAE), caused by mutations in the C1-Inh gene (C1NH), or acquired (AAE). Patients with HAE show a complement profile different from that of patients with AAE with normal levels of C1 (C1q, C1r, and C1s).
  
  
  OBJECTIVE
  We sought to characterize the complement profile of a patient with HAE and a mutation in homozygosis in the C1NH gene (c.1576T>G, Ile462Ser) and study his family.
  
  
  METHODS
  Biochemical diagnosis of HAE was confirmed by analyzing the C1NH gene. Further studies on the levels and activation states of the C1q, C1r, C1s, and C1-Inh components of the classical pathway of complement activation were also performed.
  
  
  RESULTS
  Another 7 members of the family were given diagnoses of HAE: 1 was homozygous and 6 were heterozygous for the C1NH mutation c.1576T>G. The homozygous patients showed undetectable C1q levels, reduced C1s levels, the circulating active form of C1r, and a C1-Inh mostly in its cleaved inactive form in plasma.
  
  
  CONCLUSIONS
  This is the first report of patients homozygous for a mutation affecting the coding region of C1NH. These patients showed a unique activation and consumption profile of the classical complement activation pathway different from that commonly observed in patients with HAE but similar to that of patients with AAE.
  
  
  CONCLUSIONS
  The most common HAE treatment is attenuated androgens, which increase the C1NH gene transcription levels. Because the homozygous patients lack a wild-type allele, long-term prophylactic treatment with attenuated androgens might not be advisable.
authors.affiliation: Unidad de Inmunología, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Blanch
authors.forename: Olga
authors.initials: O
authors.lastname: Roche
authors.forename: Ignacio
authors.initials: I
authors.lastname: Urrutia
authors.forename: Pedro
authors.initials: P
authors.lastname: Gamboa
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fontán
authors.forename: Margarita
authors.initials: M
authors.lastname: López-Trascasa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000799:Angioedema / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D003172:Complement C1 / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005796:Genes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D010375:Pedigree
chemical_list: D003172:Complement C1; D050718:Complement C1 Inhibitor Protein