Unraveling the complex genetics of atypical hemolytic uremic syndrome

摘要: Atypical hemolytic uremic syndrome (aHUS) is characterized by acute renal failure, thrombocytopenia, and microangiopathic anemia. aHUS far less common more severe than typical HUS, which caused E. coli infection manifests as diarrheal illness. The pathogenesis of the disease linked to dysregulation alternative pathway complement cascade. Mutations in regulators factor H (CFH), membrane cofactor protein (MCP), B (CFB), I (CFI) have been implicated aHUS. These loss or gain function mutations lead uncontrolled activity immune-mediated host cell damage. Establishing a genetic etiology important it helps direct treatment during phase when transplantation considered. It has shown previous studies that age onset well severity correlated with type mutation patient found carry. In forty percent patients CFH, MCP, CFB, CFI, C3 THBD not detected. data strongly suggest other factors are involved comprehensive detection essential provide diagnostic prognostic information, improve their clinical care. My thesis work aimed identify contributors this disease. To achieve goal we began screening largest American cohort for C3, CFHR5. This study identified over thirty novel suggests method would better serve patients. these multiplex ligation-dependent probe amplification was used detect