Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

Veronique Frémeaux-Bacchi; Elizabeth C. Miller; M. Kathryn Liszewski; Lisa Strain; Jacques Blouin; Alison L. Brown; Nadeem Moghal; Bernard S. Kaplan; Robert A. Weiss; Karl Lhotta; Gaurav Kapur; Tej Mattoo; Hubert Nivet; William Wong; Sophie Gie; Bruno Hurault De Ligny; Michel Fischbach; Ritu Gupta; Richard Hauhart; Vincent Meunier; Chantal Loirat; Marie Agnès Dragon-Durey; Wolf H. Fridman; Bert J.C. Janssen; Timothy H.J. Goodship; John P. Atkinson

doi:10.1182/blood-2008-01-133702

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

Veronique Frémeaux-Bacchi, Elizabeth C. Miller, M. Kathryn Liszewski, Lisa Strain, Jacques Blouin, Alison L. Brown, Nadeem Moghal, Bernard S. Kaplan, Robert A. Weiss, Karl Lhotta, Gaurav Kapur, Tej Mattoo, Hubert Nivet, William Wong, Sophie Gie, Bruno Hurault De Ligny, Michel Fischbach, Ritu Gupta, Richard Hauhart, Vincent MeunierChantal Loirat, Marie Agnès Dragon-Durey, Wolf H. Fridman, Bert J.C. Janssen, Timothy H.J. Goodship, John P. Atkinson

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Abstract

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dys-regulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.

Original language	English
Pages (from-to)	4948-4952
Number of pages	5
Journal	Blood
Volume	112
Issue number	13
DOIs	https://doi.org/10.1182/blood-2008-01-133702
State	Published - Dec 15 2008

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Frémeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., Nivet, H., Wong, W., Gie, S., De Ligny, B. H., Fischbach, M., Gupta, R., Hauhart, R., ... Atkinson, J. P. (2008). Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood, 112(13), 4948-4952. https://doi.org/10.1182/blood-2008-01-133702

@article{c8af9993272545e3b63b212935b1495b,

title = "Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome",

abstract = "Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dys-regulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.",

author = "Veronique Fr{\'e}meaux-Bacchi and Miller, {Elizabeth C.} and Liszewski, {M. Kathryn} and Lisa Strain and Jacques Blouin and Brown, {Alison L.} and Nadeem Moghal and Kaplan, {Bernard S.} and Weiss, {Robert A.} and Karl Lhotta and Gaurav Kapur and Tej Mattoo and Hubert Nivet and William Wong and Sophie Gie and {De Ligny}, {Bruno Hurault} and Michel Fischbach and Ritu Gupta and Richard Hauhart and Vincent Meunier and Chantal Loirat and Dragon-Durey, {Marie Agn{\`e}s} and Fridman, {Wolf H.} and Janssen, {Bert J.C.} and Goodship, {Timothy H.J.} and Atkinson, {John P.}",

year = "2008",

month = dec,

day = "15",

doi = "10.1182/blood-2008-01-133702",

language = "English",

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pages = "4948--4952",

journal = "Blood",

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publisher = "Blood",

number = "13",

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Frémeaux-Bacchi, V, Miller, EC, Liszewski, MK, Strain, L, Blouin, J, Brown, AL, Moghal, N, Kaplan, BS, Weiss, RA, Lhotta, K, Kapur, G, Mattoo, T, Nivet, H, Wong, W, Gie, S, De Ligny, BH, Fischbach, M, Gupta, R, Hauhart, R, Meunier, V, Loirat, C, Dragon-Durey, MA, Fridman, WH, Janssen, BJC, Goodship, THJ & Atkinson, JP 2008, 'Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome', Blood, vol. 112, no. 13, pp. 4948-4952. https://doi.org/10.1182/blood-2008-01-133702

TY - JOUR

T1 - Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

AU - Frémeaux-Bacchi, Veronique

AU - Miller, Elizabeth C.

AU - Liszewski, M. Kathryn

AU - Strain, Lisa

AU - Blouin, Jacques

AU - Brown, Alison L.

AU - Moghal, Nadeem

AU - Kaplan, Bernard S.

AU - Weiss, Robert A.

AU - Lhotta, Karl

AU - Kapur, Gaurav

AU - Mattoo, Tej

AU - Nivet, Hubert

AU - Wong, William

AU - Gie, Sophie

AU - De Ligny, Bruno Hurault

AU - Fischbach, Michel

AU - Gupta, Ritu

AU - Hauhart, Richard

AU - Meunier, Vincent

AU - Loirat, Chantal

AU - Dragon-Durey, Marie Agnès

AU - Fridman, Wolf H.

AU - Janssen, Bert J.C.

AU - Goodship, Timothy H.J.

AU - Atkinson, John P.

PY - 2008/12/15

Y1 - 2008/12/15

N2 - Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dys-regulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.

AB - Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dys-regulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.

UR - http://www.scopus.com/inward/record.url?scp=54049137505&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-01-133702

DO - 10.1182/blood-2008-01-133702

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AN - SCOPUS:54049137505

SN - 0006-4971

VL - 112

SP - 4948

EP - 4952

JO - Blood

JF - Blood

IS - 13

ER -

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

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