Classification

 nondiarrheal, nonverocytotoxin SHU (atypical SHU)

Etiology

 nondiarrheal, nonverocytotoxin SHU (atypical SHU)

• mutations in the complement regulator factor-H in 15-30% of patients with atypical hemolytic uremic syndrome (HUS)(#12424708#)

 mutations of the CD46 gene in atypical hemolytic uremic syndrome (HUS)

• heterozygous deletion resulting in the intracellular retention of the mutant protein
• different heterozygous deletion leading to a premature stop codon and the loss of the C-terminus
• substitution (S206P) resulting in cell-surface expression but inefficient inactivation of surface-bound C3b

Membrane cofactor protein (MCP, CD46) is a widely expressed transmembrane complement regulator. As does the soluble regulator factor-H, it inhibits complement activation by inactivating the C3b that is deposited on target membranes.

References

 Goodship TH, Liszewski MK, Kemp EJ, Richards A, Atkinson JP. Mutations in CD46, a complement regulatory protein, predispose to atypical HUS. Trends Mol Med. 2004 May 1;10(5):226-231. PMID: #15121049#