Mutations in CD46, a complement regulatory protein, predispose to atypical HUS.

Abstract

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. Factor H mutations have been described in 15-30% of patients with atypical haemolytic uraemic syndrome (HUS). Recent studies have identified mutations in the MCP gene in four families. In one, a heterozygous deletion resulted in the intracellular retention of the mutant protein. In another, a different heterozygous deletion led to a premature stop codon and the loss of the C-terminus. In the other two, a substitution (S206P) resulted in cell-surface expression but inefficient inactivation of surface-bound C3b. These findings provide further evidence that complement dysregulation predisposes to the development of HUS.

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@article{Goodship2004MutationsIC, title={Mutations in CD46, a complement regulatory protein, predispose to atypical HUS.}, author={Timothy H. J. Goodship and M. Kathryn Liszewski and Elizabeth J Kemp and Anna Richards and John P Atkinson}, journal={Trends in molecular medicine}, year={2004}, volume={10 5}, pages={226-31} }