We performed sequence analysis of the complement genes complement factor H (CFH), complement factor I (CFI), and complement C3 (C3) in 866 aHUS/C3G and 697 AMD patients.
Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes.
Five of these patients had risk variants in MCP or CFI that were previously identified in atypical hemolytic uremic syndrome, a disease characterized by endothelial damage.
In conclusion, mutations in complement factor I affect both secretion and function of FI, which leads to impaired regulation of the complement system in aHUS.