Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.

ABSTRACT: Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations in one or more genes encoding complement-regulatory proteins have been reported in approximately one-third of nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect in the protection of cell surfaces against complement activation in susceptible individuals. Here, we identified a subgroup of aHUS patients showing persistent activation of the complement alternative pathway and found within this subgroup two families with mutations in the gene encoding factor B (BF), a zymogen that carries the catalytic site of the complement alternative pathway convertase (C3bBb). Functional analyses demonstrated that F286L and K323E aHUS-associated BF mutations are gain-of-function mutations that res

SUBMITTER: Goicoechea de Jorge E 

PROVIDER: S-EPMC1765442 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature