title: Factors determining penetrance in familial atypical haemolytic uraemic syndrome.
abstract: BACKGROUND
  Inherited abnormalities of complement are found in ∼60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643C>G; p. Arg1215Gly) in whom a common lineage is probable. 25 individuals have been affected with aHUS with three peaks of incidence-early childhood (n=6), early adulthood (n=11) and late adulthood (n=8). Eighteen individuals who have not developed aHUS carry the mutation.
  
  
  METHODS
  We estimated penetrance at the ages of 4, 27, 60 and 70 years as both a binary and a survival trait using MLINK and Mendel. We genotyped susceptibility factors in CFH, CD46 and CFHR1 in affected and unaffected carriers.
  
  
  CONCLUSIONS
  We found that the estimates of penetrance at the age of 4 years ranged from <0.01 to 0.10, at the age of 27 years from 0.16 to 0.29, at the age of 60 years from 0.39 to 0.51 and at the age of 70 years from 0.44 to 0.64. We found that the CFH haplotype on the allele not carrying the CFH mutation had a significant effect on disease penetrance. In this family, we did not find that the CD46 haplotypes had a significant effect on penetrance.
authors.affiliation: Peninsula Clinical Genetics Service, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Heavitree), Exeter, UK University of Exeter Medical School, University of Exeter, Exeter, UK Bristol Clinical Genetics Service, University Hospitals Bristol NHS Foundation Trust, Clinical Genetics, St. Michael's Hospital, Bristol, UK.
authors.forename: Francis H
authors.initials: FH
authors.lastname: Sansbury
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK Department of Renal Medicine, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Wonford), Exeter, UK.
authors.forename: Coralie
authors.initials: C
authors.lastname: Bingham
authors.affiliation: Peninsula Clinical Genetics Service, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Heavitree), Exeter, UK.
authors.forename: Gilly
authors.initials: G
authors.lastname: Bromilow
authors.affiliation: Department of Renal Medicine, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Wonford), Exeter, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Nicholls
authors.affiliation: Research Design Service South West, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Wonford), Exeter, UK.
authors.forename: Roy
authors.initials: R
authors.lastname: Powell
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Bev
authors.initials: B
authors.lastname: Shields
authors.affiliation: Department of Renal Medicine, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Wonford), Exeter, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Smyth
authors.affiliation: Lister Renal Units, East and North Hertfordshire NHS Trust, Stevenage, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Warwicker
authors.affiliation: Northern Molecular Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Strain
authors.affiliation: Northern Molecular Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Wilson
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Goodship
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Timothy H J
authors.initials: TH
authors.lastname: Goodship
authors.affiliation: Peninsula Clinical Genetics Service, Royal Devon & Exeter NHS Foundation Trust, Royal Devon & Exeter Hospital (Heavitree), Exeter, UK University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Turnpenny
mesh_terms: D000328:Adult; D000368:Aged; D065766:Atypical Hemolytic Uremic Syndrome / Q000235:genetics*; D002675:Child, Preschool; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance
chemical_list: D017242:Complement Factor H
keywords: Clinical genetics; Renal Medicine