title: Coagulation Factor XII Gene Mutation in Brazilian Families with Hereditary Angioedema with Normal C1 Inhibitor.
abstract: BACKGROUND
  Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare disorder. Mutations of the gene encoding coagulation factor XII have been identified in a subset of patients with this condition. Our aim was to investigate mutations in the F12 gene in patients with HAE with normal C1-INH from Brazil.
  
  
  METHODS
  We studied 5 Brazilian families with index female patients who presented with recurrent angioedema with normal C1-INH and C4 levels. Genomic DNA was isolated from whole blood and PCR was performed. Mutations were detected by the sequencing of exon 9 of the F12 gene and allelic discrimination.
  
  
  RESULTS
  The c.983C>A (p.Thr328Lys) mutation was identified in 16 subjects, from 4 of the 5 families studied, including 8 patients with symptoms of HAE with normal C1-INH (87.5% women) and 8 subjects asymptomatic for HAE (25% women). Mean age at onset of symptoms among the FXII-HAE patients was 13.8 years (range 6-25 years). Recurrent abdominal pain (100%) and subcutaneous angioedema (87.5%) were the most frequent clinical presentations. Two patients presented with associated laryngeal edema. In keeping with previous observations in patients with both C1-INH-HAE and HAE with normal C1-INH, all 7 women with FXII-HAE reported triggering or worsening of symptoms upon intake of estrogen-containing oral contraceptives and/or pregnancy.
  
  
  CONCLUSIONS
  We report for the first time in Brazil a mutation in the F12 gene as a likely cause of HAE with normal C1-INH in patients with recurrent attacks of angioedema and/or abdominal pain. A higher frequency of abdominal pain attacks and onset of symptoms at a younger age were observed among Brazilian patients when compared to those from other parts of the world.
authors: Department of Medicine, Ribeirão Preto Medical School, Ribeirão Preto, Brazil.
authors: Adriana S
authors: AS
authors: Moreno
authors: Solange O R
authors: SO
authors: Valle
authors: Soloni
authors: S
authors: Levy
authors: Alfeu T
authors: AT
authors: França
authors: Faradiba S
authors: FS
authors: Serpa
authors: Helen A
authors: HA
authors: Arcuri
authors: Mario S
authors: MS
authors: Palma
authors: Wagner N
authors: WN
authors: Campos
authors: Marina M
authors: MM
authors: Dias
authors: Denise
authors: D
authors: Ponard
authors: Nicole
authors: N
authors: Monnier
authors: Joel
authors: J
authors: Lunardi
authors: Konrad
authors: K
authors: Bork
authors: Wilson Araujo
authors: WA
authors: Silva
authors: L Karla
authors: LK
authors: Arruda
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D054179:Angioedemas, Hereditary / Q000097:blood / Q000235:genetics* / Q000276:immunology; D001938:Brazil; D003174:Complement C1 Inactivator Proteins / Q000276:immunology*; D050718:Complement C1 Inhibitor Protein; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005174:Factor XII / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D005174:Factor XII; D004247:DNA