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. Epub 2008 Sep 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Codon, Nonsense
  • Complement C3 / analysis
  • Complement C3 / genetics*
  • DNA Mutational Analysis
  • Genetic Predisposition to Disease
  • Hemolytic-Uremic Syndrome / etiology
  • Hemolytic-Uremic Syndrome / genetics*
  • Hemolytic-Uremic Syndrome / immunology
  • Heterozygote
  • Humans
  • Infant
  • Mutation*
  • Mutation, Missense
  • Young Adult

Substances

  • Codon, Nonsense
  • Complement C3