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

被引：308

作者：

Fremeaux-Bacchi, Veronique ^{[1
,2
]}

Miller, Elizabeth C. ^{[3
]}

Liszewski, M. Kathryn ^{[3
]}

Strain, Lisa ^{[4
]}

Blouin, Jacques ^{[1
,2
]}

Brown, Alison L. ^{[5
]}

Moghal, Nadeem ^{[6
]}

Kaplan, Bernard S. ^{[7
]}

Weiss, Robert A. ^{[8
]}

Lhotta, Karl ^{[9
]}

Kapur, Gaurav ^{[10
]}

Mattoo, Tej

Nivet, Hubert ^{[11
]}

Wong, William ^{[12
]}

Gie, Sophie ^{[13
]}

de Ligny, Bruno Hurault ^{[14
]}

Fischbach, Michel ^{[15
]}

Gupta, Ritu ^{[3
]}

Hauhart, Richard ^{[3
]}

Meunier, Vincent ^{[16
]}

Loirat, Chantal ^{[17
]}

Dragon-Durey, Marie-Agnes ^{[1
,2
]}

Fridman, Wolf H. ^{[1
,2
]}

Janssen, Bert J. C. ^{[18
]}

Goodship, Timothy H. J. ^{[19
]}

Atkinson, John P. ^{[3
]}

机构：

[1] Hop Europeen Georges Pompidou, Serv Immunol Biol, F-75908 Paris 15, France

[2] Cordeliers Res Ctr, INSERM, UMRS 872, Paris, France

[3] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO USA

[4] Newcastle Tyne Hosp, Natl Hlth Serv Fdn Trust, No Mol Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England

[5] Newcastle Tyne Hosp, Natl Hlth Serv Fdn Trust, Dept Renal Med, Newcastle Upon Tyne, Tyne & Wear, England

[6] Newcastle Tyne Hosp, Natl Hlth Serv Fdn Trust, Dept Paediat Nephrol, Newcastle Upon Tyne, Tyne & Wear, England

[7] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA USA

[8] Maria Fareri Childrens Hosp, Westchester Med Ctr, Valhalla, NY USA

[9] Univ Innsbruck Hosp, Dept Internal Med, Div Clin Nephrol, A-6020 Innsbruck, Austria

[10] Childrens Hosp Michigan, Detroit, MI 48201 USA

[11] Ctr Hosp Tours, Unite Nephrol Pediat, Tours, France

[12] Starship Childrens Hosp, Auckland, New Zealand

[13] CHU Rennes, Dept Med Enfant & Adolescent, Hop Sud, Rennes, France

[14] Hop Clemenceau, Serv Nephrol Transplantat Renale, Caen, France

[15] Hop Hautepierre, Serv Pediat, Strasbourg, France

[16] Hop Robert Boulin, Serv Med Interne, Libourne, France

[17] Hop Robert Debre, Serv Nephrol Pediat, F-75019 Paris, France

[18] Univ Utrecht, Bijvoet Ctr Biomol Res, Fac Sci, Utrecht, Netherlands

[19] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England

来源：

BLOOD | 2008年 / 112卷 / 13期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

D O I：

10.1182/blood-2008-01-133702

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2008; 112: 4948-4952)

引用

页码：4948 / 4952

页数：5

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