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Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome
Author(s) -
Maga Tara K.,
Nishimura Carla J.,
Weaver Amy E.,
Frees Kathy L.,
Smith Richard J.H.
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21256
Subject(s) - atypical hemolytic uremic syndrome , alternative complement pathway , cd46 , microangiopathic hemolytic anemia , complement system , eculizumab , biology , complement factor i , complement factor b , immunology , population , factor h , mutation , genetics , gene , medicine , thrombotic thrombocytopenic purpura , antibody , platelet , environmental health
Atypical hemolytic uremic syndrome (aHUS) is characterized by acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia, and occurs with an estimated incidence in the USA of 2 per 1,000,000. Disease pathogenesis is related to dysregulation of the alternative pathway (AP) of the complement cascade at the level of the cell membrane secondary to mutations in a number of complement genes including complement factor H (CFH), complement factor H‐related 5 (CFHR5), complement factor I (CFI), CD46 (MCP), complement factor B (CFB), complement component 3 (C3) and thrombomodulin (THBD). Since aHUS is rare, mutation rate data in large patient cohorts are scarce. Here we present the first cohort of American patients in whom mutation screening was completed on all genes currently implicated in aHUS. In addition to identifying a number of novel variants, we provide information on the relative frequency of mutations in these genes in an American aHUS population. Twelve percent (12%) of patients carrying disease‐associated genetic variants segregated mutations in more than one gene mandating comprehensive genetic testing in the diagnosis and management of these patients. ©2010 Wiley‐Liss, Inc.