title: Novel and recurrent mutations in the C1NH gene of Arab patients affected with hereditary angioedema.
abstract: BACKGROUND
  Autosomal dominant hereditary angioedema (HAE) results in episodes of subcutaneous edema in any body part and/or submucosal edema of the upper respiratory or gastrointestinal tracts. This disorder is caused by mutations in the C1NH gene, many of which have been described primarily in European patients. However, the genetic cause of HAE in Middle Eastern Arab patients has not yet been determined.
  
  
  METHODS
  Four unrelated Arab families, in which 15 patients were diagnosed with HAE, were studied. DNA from 13 patients was analyzed for mutations in the C1NH gene by DNA sequencing.
  
  
  RESULTS
  Three novel and 2 recurrent mutations were identified in the C1NH gene of HAE patients. In family 1, the patient was heterozygous for a novel c.856C>T and a recurrent c.1361T>A missense mutation encoding for p.Arg264Cys and p.Val432Glu, respectively. In patients from family 2, a novel c.509C>T missense mutation encoding for a p.Ser148Phe was identified. In patients from family 3, a novel c.1142delC nonsense mutation encoding for a p.Ala359AlafsX15 was discovered. In family 4, a recurrent c.1397G>A missense mutation encoding for a p.Arg444His was present.
  
  
  CONCLUSIONS
  This is the first ever report of C1NH gene mutations in Middle Eastern Arab patients. Our study suggests that, despite the numerous existing mutations in the C1NH gene, there are novel and recurrent mutations in HAE patients of non-European origin. We conclude that the spectrum of C1NH gene mutations in HAE patients is wider due to the likely presence of novel and recurrent mutations in patients of other ethnicities.
authors.affiliation: Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. MFHaque@Kfshrc.edu.sa
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faiyaz-Ul-Haque
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Al-Gazlan
authors.forename: Halah A
authors.initials: HA
authors.lastname: Abalkhail
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Abdulatif
authors.forename: Mohamed
authors.initials: M
authors.lastname: Toulimat
authors.forename: Iskra
authors.initials: I
authors.lastname: Peltekova
authors.forename: Agha M R
authors.initials: AM
authors.lastname: Khaliq
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Syed H E
authors.initials: SH
authors.lastname: Zaidi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018912:Arabs / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D003174:Complement C1 Inactivator Proteins / Q000235:genetics* / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003613:Danazol / Q000627:therapeutic use; D005260:Female; D056829:Hereditary Angioedema Types I and II / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008877:Middle East; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003176:Complement C3; D003181:Complement C4; C469952:SERPING1 protein, human; D003613:Danazol