Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

  • Blood. 2008 Dec 15;112(13):4948-52. doi: 10.1182/blood-2008-01-133702.
Veronique Frémeaux-Bacchi  1 ,  Elizabeth C Miller ,  M Kathryn Liszewski ,  Lisa Strain ,  Jacques Blouin ,  Alison L Brown ,  Nadeem Moghal ,  Bernard S Kaplan ,  Robert A Weiss ,  Karl Lhotta ,  Gaurav Kapur ,  Tej Mattoo ,  Hubert Nivet ,  William Wong ,  Sophie Gie ,  Bruno Hurault de Ligny ,  Michel Fischbach ,  Ritu Gupta ,  Richard Hauhart ,  Vincent Meunier ,  Chantal Loirat ,  Marie-Agnès Dragon-Durey ,  Wolf H Fridman ,  Bert J C Janssen ,  Timothy H J Goodship ,  John P Atkinson
Affiliations
  • 1. Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.
PMID: 18796626 DOI: 10.1182/blood-2008-01-133702
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.