title: A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family.
abstract: BACKGROUND
  Hereditary angioedema is an autosomal dominant disease characterized by episodes of subcutaneous and submucosal edema. It is caused by deficiency of the C1 inhibitor protein, leading to elevated levels of bradykinin. More than 200 mutations in C1 inhibitor gene have been reported. The aim of this study was to analyze clinical features of a large family with an index case of hereditary angioedema and to determine the disease-causing mutation in this family.
  
  
  METHODS
  Family pedigree was constructed with 275 individuals distributed in five generations. One hundred and sixty-five subjects were interviewed and investigated for mutation at the C1 inhibitor gene. Subjects reporting a history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for hereditary angioedema.
  
  
  RESULTS
  We have identified a novel mutation at the C1 inhibitor gene, c.351delC, which is a single-nucleotide deletion of a cytosine on exon 3, resulting in frameshift with premature stop codon. Sequencing analysis of the hypothetical truncated C1 inhibitor protein allowed us to conclude that, if transcription occurs, this protein has no biological activity. Twenty-eight members of the family fulfilled diagnostic criteria for hereditary angioedema and all of them presented the c.351delC mutation. Variation in clinical presentation and severity of disease was observed among these patients. One hundred and thirty-seven subjects without hereditary angioedema did not have the c.351delC mutation.
  
  
  CONCLUSIONS
  The present study provides definitive evidence to link a novel genetic mutation to the development of hereditary angioedema in patients from a Brazilian family.
authors.affiliation: Department of Pediatrics, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Ferraro
authors.forename: A S
authors.initials: AS
authors.lastname: Moreno
authors.forename: E C
authors.initials: EC
authors.lastname: Castelli
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
authors.forename: M S
authors.initials: MS
authors.lastname: Palma
authors.forename: H A
authors.initials: HA
authors.lastname: Arcuri
authors.forename: A P
authors.initials: AP
authors.lastname: Lange
authors.forename: K
authors.initials: K
authors.lastname: Bork
authors.forename: W
authors.initials: W
authors.lastname: Sarti
authors.forename: L K
authors.initials: LK
authors.lastname: Arruda
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D054179:Angioedemas, Hereditary / Q000235:genetics*; D001483:Base Sequence; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003174:Complement C1 Inactivator Proteins / Q000235:genetics* / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4 / Q000378:metabolism; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; C469952:SERPING1 protein, human