A novel deletion in the RCA gene cluster causes atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is a complex complement-mediated disease that progresses to end-stage renal failure (ESRF) in 50% of cases. Dysregulation of the alternative pathway (AP) of the complement cascade manifests as microangiopathic anaemia and thrombocytopenia. Multiple genes in the AP have been implicated in disease pathogenesis. Here, we report the clinical presentation of an affected patient that was inconsistent with genotype-phenotype data for carriers of CD46 mutations. Tests of AP function in this patient suggested additional genetic factors, and in-depth studies revealed a de novo heterozygous deletion that creates a novel CFH/CFHR1 fusion protein.