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 Meunier

Chantal Loirat, Marie-Agnès Dragon-Durey, Wolf H Fridman, Bert J C Janssen, Timothy H J Goodship, John P Atkinson

Service d'Immunologie Biologique

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. 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)	4948-52
Number of pages	5
Journal	Blood
Volume	112
Issue number	13
DOIs	https://doi.org/10.1182/blood-2008-01-133702
Publication status	Published - 15 Dec 2008

Keywords

Adolescent
Adult
Child
Child, Preschool
Codon, Nonsense
Complement C3/analysis
DNA Mutational Analysis
Genetic Predisposition to Disease
Hemolytic-Uremic Syndrome/etiology
Heterozygote
Humans
Infant
Mutation
Mutation, Missense
Young Adult

Access to Document

10.1182/blood-2008-01-133702

Cite this

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., Hurault de Ligny, B., 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), 4948-52. https://doi.org/10.1182/blood-2008-01-133702

@article{a79e7b2d6bc2468fb01cca1291c29794,

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

abstract = "Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. 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.",

keywords = "Adolescent, Adult, Child, Child, Preschool, Codon, Nonsense, Complement C3/analysis, DNA Mutational Analysis, Genetic Predisposition to Disease, Hemolytic-Uremic Syndrome/etiology, Heterozygote, Humans, Infant, Mutation, Mutation, Missense, Young Adult",

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 \{Hurault de Ligny\}, Bruno and Michel Fischbach and Ritu Gupta and Richard Hauhart and Vincent Meunier and Chantal Loirat and Marie-Agn{\`e}s Dragon-Durey 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",

volume = "112",

pages = "4948--52",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier BV",

number = "13",

}

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, Hurault de Ligny, B, Fischbach, M, Gupta, R, Hauhart, R, Meunier, V, Loirat, C, Dragon-Durey, M-A, 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. 4948-52. 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 - Hurault de Ligny, Bruno

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 dysregulation. 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 dysregulation. 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.

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - Codon, Nonsense

KW - Complement C3/analysis

KW - DNA Mutational Analysis

KW - Genetic Predisposition to Disease

KW - Hemolytic-Uremic Syndrome/etiology

KW - Heterozygote

KW - Humans

KW - Infant

KW - Mutation

KW - Mutation, Missense

KW - Young Adult

U2 - 10.1182/blood-2008-01-133702

DO - 10.1182/blood-2008-01-133702

M3 - Article

C2 - 18796626

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this