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Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome

Lookup NU author(s): Professor David KavanaghORCiD, Dr Liz Kemp, Professor Judith Goodship, Professor Tim Goodship


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Mutations in the plasma complement regulator factor H (CFH) and the transmembrane complement regulator membrane co-factor protein (MCP) have been shown to predispose to atypical hemolytic uremic syndrome (HUS). Both of these proteins act as co-factors for complement factor I (IF). IF is a highly specific serine protease that cleaves the α-chains of C3b and C4b and thus downregulates activation of both the classical and the alternative complement pathways. This study looked for IF mutations in a panel of 76 patients with HUS. Mutations were detected in two patients, both of whom had reduced serum IF levels. A heterozygous bp change, c.463 G > A, which results in a premature stop codon (W127X), was found in one, and in the other, a heterozygous single base pair deletion in exon 7 (del 922C) was detected. Both patients had a history of recurrent HUS after transplantation. This is in accordance with the high rate of recurrence in patients with CFH mutations. Patients who are reported to have mutations in MCP, by contrast, do not have recurrence after transplantation. As with CFH- and MCP-associated HUS, there was incomplete penetrance in the family of one of the affected individuals. This study provides further evidence that atypical HUS is a disease of complement dysregulation. Copyright © 2005 by the American Society of Nephrology.

Publication metadata

Author(s): Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G, Richards A, Ward R, Goodship JA, Goodship THJ

Publication type: Article

Publication status: Published

Journal: Journal of the American Society of Nephrology

Year: 2005

Volume: 16

Issue: 7

Pages: 2150-2155

ISSN (print): 1046-6673

ISSN (electronic): 1555-905X

Publisher: American Society of Nephrology


DOI: 10.1681/ASN.2005010103

PubMed id: 15917334


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