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

• Published in: Nephrology, dialysis, transplantation Vol. 26; no. 2; pp. 739 - 741
• Main Authors: MAGA, Tara K, MEYER, Nicole C, BELSHA, Craig, NISHIMURA, Carla J, YUZHOU ZHANG, SMITH, Richard J. H
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2011
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Atypical Hemolytic Uremic Syndrome; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Complement C3b Inactivator Proteins - genetics; Emergency and intensive care: renal failure. Dialysis management; Exceptional Case; Hemolytic-Uremic Syndrome - genetics; Humans; Infant; Intensive care medicine; Male; Medical sciences; Membrane Cofactor Protein; Multigene Family - genetics; Pharmacology. Drug treatments; Sequence Deletion; Kidney disease; Thrombocytopenia; Urinary system disease; Hemolytic uremic syndrome; Hemodialysis; Acute; kidney transplantation; aHUS; Hemopathy; Complement; Extrarenal dialysis; Platelet; Hemolytic anemia; Renal failure; Deletion
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfq658

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.