title: Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency.
abstract: BACKGROUND
  Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype-phenotype relationship does not seem to exist in HAE, although the polymorphism c.-21T>C of exon 2 has been reported to be associated with a more severe phenotype. We aimed to establish the mutational spectrum of C1 inhibitor deficiency in Denmark and investigate the possible disease-aggravating effect of the c.-21T>C polymorphism.
  
  
  METHODS
  Hereditary angioedema was diagnosed based on clinical features and C1 inhibitor deficiency. A general severity score ranging from 0 to 10 was developed based on age at disease onset, clinical manifestations and treatment experiences. SERPING1 gene investigation was performed by exon sequencing followed by multiplex ligation-dependent probe amplification genomic rearrangement analysis in all known Danish HAE families.
  
  
  RESULTS
  Fifty-nine patients with HAE from 26 families were included in this study. The mean disease severity score was 7.12 [1-10], and the mean C1 inhibitor function was 26% [20-46%]. The sensitivity of the mutational screening was 96%, and 13 new mutations were found in this Danish patient cohort. Nine patients (15%) carried the c.-21T>C polymorphism, but they didn't have a more severe phenotype.
  
  
  CONCLUSIONS
  Thirteen new mutations were identified in the Danish HAE population. No correlation between the c.-21T>C polymorphism, the biochemical values of C1 inhibitor function and the clinical severity score was found.
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark. anette.bygum@hae.dk
authors.forename: A
authors.initials: A
authors.lastname: Bygum
authors.forename: C R
authors.initials: CR
authors.lastname: Fagerberg
authors.forename: D
authors.initials: D
authors.lastname: Ponard
authors.forename: N
authors.initials: N
authors.lastname: Monnier
authors.forename: J
authors.initials: J
authors.lastname: Lunardi
authors.forename: C
authors.initials: C
authors.lastname: Drouet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D050718:Complement C1 Inhibitor Protein / Q000235:genetics*; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein