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.
Maga
Tara K
TK
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Meyer
Nicole C
NC
Belsha
Craig
C
Nishimura
Carla J
CJ
Zhang
Yuzhou
Y
Smith
Richard J H
RJ
D065766:Atypical Hemolytic Uremic Syndrome; D003180:Complement C3b Inactivator Proteins / Q000235:genetics*; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D051916:Membrane Cofactor Protein; D005810:Multigene Family / Q000235:genetics; D017384:Sequence Deletion
C497857:CD46 protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D051916:Membrane Cofactor Protein