Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.
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.
Frémeaux-Bacchi
Veronique
V
Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
Miller
Elizabeth C
EC
Liszewski
M Kathryn
MK
Strain
Lisa
L
Blouin
Jacques
J
Brown
Alison L
AL
Moghal
Nadeem
N
Kaplan
Bernard S
BS
Weiss
Robert A
RA
Lhotta
Karl
K
Kapur
Gaurav
G
Mattoo
Tej
T
Nivet
Hubert
H
Wong
William
W
Gie
Sophie
S
Hurault de Ligny
Bruno
B
Fischbach
Michel
M
Gupta
Ritu
R
Hauhart
Richard
R
Meunier
Vincent
V
Loirat
Chantal
C
Dragon-Durey
Marie-Agnès
MA
Fridman
Wolf H
WH
Janssen
Bert J C
BJ
Goodship
Timothy H J
TH
Atkinson
John P
JP
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
D018389:Codon, Nonsense; D003176:Complement C3
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