title: Genetic disorders in complement (regulating) genes in patients with atypical haemolytic uraemic syndrome (aHUS).
abstract: BACKGROUND
  Atypical HUS (aHUS) is thought to be caused by predisposing mutations in genes encoding complement (regulating) proteins, such as Factor H (CFH), Factor I (IF), membrane co-factor protein (MCP) and Factor B (FB), or by auto-antibodies against CFH (alphaFH) in combination with a homozygous polymorphic deletion of the genes encoding Complement Factor H-related 1 and 3 (DeltaCFHR1/3). The clinical impact of this knowledge is high, as it might be a prognostic factor for the outcome of renal transplantations and kidney donations.
  
  
  METHODS
  Mutational screening, by means of PCR and DNA sequencing, is performed in the above-mentioned genes in a group of 72 aHUS patients. Also, the presence of alphaFH and DeltaCFHR1/3 was tested in patients and controls.
  
  
  RESULTS
  In 23 patients, a genetic aberration in at least one gene or the presence of alphaFH was found. A heterozygous mutation was observed in CFH in nine patients, in IF in seven patients and in MCP in three patients. No mutations were observed in FB. Seven patients presented alphaFH, of whom five also carried DeltaCFHR1/3. Three patients carried a combined mutation (two patients: IF and MCP; one patient: IF, alphaFH and DeltaCFHR1/3). A significant difference between patients and controls was detected for the presence of all three associated polymorphisms in CFH.
  
  
  CONCLUSIONS
  Genetic abnormalities or the presence of alphaFH were detected in 31.9% of the aHUS patients. Furthermore, bigenic mutations were present, indicating that routine DNA mutation analysis of all complement factors associated with aHUS is important.
authors.affiliation: Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre (RUNMC), P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Dineke
authors.initials: D
authors.lastname: Westra
authors.forename: Elena
authors.initials: E
authors.lastname: Volokhina
authors.forename: Eefje
authors.initials: E
authors.lastname: van der Heijden
authors.forename: Annemieke
authors.initials: A
authors.lastname: Vos
authors.forename: Marleen
authors.initials: M
authors.lastname: Huigen
authors.forename: Jitske
authors.initials: J
authors.lastname: Jansen
authors.forename: Edwin
authors.initials: E
authors.lastname: van Kaauwen
authors.forename: Thea
authors.initials: T
authors.lastname: van der Velden
authors.forename: Nicole
authors.initials: N
authors.lastname: van de Kar
authors.forename: Lambert
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D051916:Membrane Cofactor Protein; D017242:Complement Factor H; D005340:Fibrinogen; D003165:Complement System Proteins; D011415:Complement Factor B