an interactive web database of factor stronghstrong-associated hemolytic.pdfVIP

HUMAN MUTATION 27(1), 21^30, 2006 DATABASES An Interactive Web Database of Factor H- Associated Hemolytic Uremic Syndrome Mutations: Insights Into the Structural Consequences of Disease-Associated Mutations Rebecca E. Saunders,1 Timothy H.J. Goodship,2 Peter F. Zipfel,3 and Stephen J. Perkins1 1Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Darwin Building, University College London, London, United Kingdom; 2The Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; 3 ¨ Department of Infection Biology, Hans Knoll Institute for Natural Products Research, Jena, Germany Communicated by Mirelle Claustres Factor H (FH) is a central complement regulator comprised of 20 short complement repeat (SCR) domains. Nucleotide changes within this gene (CFH) have been observed in patients with hemolytic uremic syndrome (HUS), and also membranoproliferative glomerulonephritis and age-related macular degeneration. All parts of FH are affected, but many mutations are clustered in the C-terminal part of FH. Up to now, structural analyses of HUS have been based on SCR-20, a domain that is involved in FH interactions with C3b, heparin, and endothelial cells. In order to identify the structural and functional consequence of HUS mutations, further disease-associated mutations were analyzed in terms of homology and nuclear magnetic resonance (NMR) models for factor H SCR domains. An interactive web database of 54 human HUS-associated mutations and others was created from the literature (www.FH-HUS.org). This has comprehensive search and analysis tools, integrating phenotypic and genetic data with structural analysis. Each mutation can be highlighted on the