title: Hereditary angioedema with normal C1-INH with versus without specific F12 gene mutations.
abstract: BACKGROUND
  Hereditary angioedema with normal C1-INH may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or mutations in genes that are still unknown (HAE-unknown). To assess the differences in transmission and inheritance, clinical features, and laboratory parameters between patients with HAE-FXII and HAE-unknown.
  
  
  METHODS
  Sixty-nine patients with HAE-FXII from 23 unrelated families and 196 patients with HAE-unknown from 65 unrelated families were studied.
  
  
  RESULTS
  Both HAE-FXII and HAE-unknown are inherited as autosomal-dominant traits with incomplete penetrance. The male to female ratio was 1 : 68 in HAE-FXII and 1 : 6.3 in HAE-unknown. The maternal to paternal transmission ratio was 35 : 14 for HAE-FXII and 109 : 12 for HAE-unknown. Mean age at onset of clinical symptoms was 20.3 years in patients with HAE-FXII and 29.6 years in patients with HAE-unknown. The incidence of asphyxiation due to angioedema was similar for HAE-FXII and HAE-unknown. Oral contraceptives and pregnancies had a significantly higher impact on HAE-FXII than on HAE-unknown. Slightly decreased C1-INH activity and C4 concentration were observed in more patients with HAE-FXII than HAE-unknown. Tests for FXI and FXII activity, plasminogen activator inhibitor 1, and activated partial thromboplastin time showed variability but no significant differences between the groups. No abnormalities were found for C1-INH protein, C1q, alpha2-macroglobulin, antithrombin III, and angiotensin-converting enzyme. In families with HAE-FXII, the number of female offspring with F12 mutations was significantly increased and that of male offspring was significantly decreased.
  
  
  CONCLUSIONS
  HAE-FXII and HAE-unknown differ in various respects, including gender distribution, genetics, symptoms, and estrogen impact.
authors.affiliation: Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bork
authors.affiliation: University Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wulff
authors.affiliation: Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Witzke
authors.affiliation: Department of Medical Psychology and Medical Sociology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hardt
mesh_terms: D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D050718:Complement C1 Inhibitor Protein / Q000235:genetics*; D016208:Databases, Factual; D005174:Factor XII / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D011994:Recombinant Proteins / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017678:Sex Distribution; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein; D011994:Recombinant Proteins; C571093:conestat alfa; D005174:Factor XII
keywords: Angioedema; coagulation factor XII; hereditary angioedema type III; hereditary angioedema with normal C1 inhibitor; specific mutations in the F12 gene