title: Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.
abstract: Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.
authors.affiliation: Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Miller
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Liszewski
authors.forename: Lisa
authors.initials: L
authors.lastname: Strain
authors.forename: Jacques
authors.initials: J
authors.lastname: Blouin
authors.forename: Alison L
authors.initials: AL
authors.lastname: Brown
authors.forename: Nadeem
authors.initials: N
authors.lastname: Moghal
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Kaplan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weiss
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kapur
authors.forename: Tej
authors.initials: T
authors.lastname: Mattoo
authors.forename: Hubert
authors.initials: H
authors.lastname: Nivet
authors.forename: William
authors.initials: W
authors.lastname: Wong
authors.forename: Sophie
authors.initials: S
authors.lastname: Gie
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurault de Ligny
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
authors.forename: Ritu
authors.initials: R
authors.lastname: Gupta
authors.forename: Richard
authors.initials: R
authors.lastname: Hauhart
authors.forename: Vincent
authors.initials: V
authors.lastname: Meunier
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: Wolf H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Bert J C
authors.initials: BJ
authors.lastname: Janssen
authors.forename: Timothy H J
authors.initials: TH
authors.lastname: Goodship
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003176:Complement C3 / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D009154:Mutation; D020125:Mutation, Missense; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D003176:Complement C3
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