deletion of complement factor h–related genes cfhr1 and cfhr3 is associated with atypical hemolytic uremic syndrome删除补充因素h-related基因cfhr1和cfhr3与非典型溶血性尿毒症综合征.pdfVIP

Deletion of Complement Factor H–Related Genes CFHR1 and CFHR3 Is Associated with Atypical Hemolytic Uremic Syndrome 1,2 3 1 ´ ´ 1 1 2 4 Peter F. Zipfel , Matthew Edey , Stefan Heinen , Mihaly Jozsi , Heiko Richter , Joachim Misselwitz , Bernd Hoppe , 5 5 6 3 7 3 Danny Routledge , Lisa Strain , Anne E. Hughes , Judith A. Goodship , Christoph Licht , Timothy H. J. Goodship , 1* Christine Skerka 1 Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany, 2 Friedrich Schiller University, Jena, Germany, 3 Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, United Kingdom, 4 Children’s Hospital of the University of Cologne, Cologne, Germany, 5 Northern Molecular Genetics Service Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom, 6 Department of Medical Genetics, Queen’s University, Belfast, United Kingdom, 7 Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H–related 1 (CFHR1) and complement factor H–related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of ;84 kb in the RCA gene cluster, resulti