Complement Factor H Gene Abnormalities in Haemolytic Uraemic Syndrome: From Point Mutations to Hybrid Gene

A typical haemolytic uraemic syndrome (aHUS) is a rare disease involving haemolytic anaemia, thrombocytopenia, and renal failure. There is growing evidence that the disease is associated with defective control of the alternative pathway of complement [1]. Genetic abnormalities in complement regulatory proteins, including complement factor H (CFH), membrane cofactor protein, and complement factor I, have been reported in 30%, 10%, and 5% of patients with aHUS, respectively [2–4]. CFH is a plasma protein produced by the liver that acts as a central regulator in the alternative pathway of complement activation. CFH acts as a cofactor for complement factor I in the inactivation of the central complement protein C3b to form iC3b. CFH also accelerates the decay of the C3 convertase C3bBb of the alternative pathway, and competes with factor B for binding to C3b [5].