title: The spectrum of phenotypes caused by variants in the CFH gene.
abstract: Complement factor H (CFH) is a complement inhibitor, which is present as a soluble protein and attached to cell surfaces throughout the human body. As such, CFH is a key player in complement homeostasis, inhibiting excessive activation of the complement cascade, with an emphasis on the alternative pathway. The significance of CFH is demonstrated by the broad range of phenotypes associated with specific CFH gene variants. This phenotypic spectrum includes renal phenotypes, such as membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome, as well as ocular phenotypes, such as basal laminar drusen and age-related macular degeneration. In addition, several overlapping phenotypes have been described in association with CFH gene variants. The phenotypic outcome of these CFH variants depends on their differential impact on plasma- and surface-bound CFH function. Consequently, distinct genotype-phenotype correlations may be observed.
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. c.boon@ohk.umcn.nl
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.forename: Nicole C
authors.initials: NC
authors.lastname: van de Kar
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.forename: Jan E E
authors.initials: JE
authors.lastname: Keunen
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D017242:Complement Factor H / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D015593:Retinal Drusen / Q000150:complications / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D017242:Complement Factor H