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01-05-2010 | Brief Report

A novel mutation in the Complement Factor B gene (CFB) and atypical hemolytic uremic syndrome

Authors: Hanan Tawadrous, Tara Maga, Josefina Sharma, Juan Kupferman, Richard J. H. Smith, Morris Schoeneman

Published in: Pediatric Nephrology | Issue 5/2010

Abstract

We report the case of an 8-year-old girl diagnosed with atypical hemolytic uremic syndrome (aHUS) with a complement factor B (CFB) gene mutation. aHUS is a disease of complement dysregulation. In approximately 50% of patients, mutations are identified in genes encoding regulators of complement—complement factor H (CFH), membrane cofactor protein or complement factor I (CFI)—or activators of complement—complement factor B (CFB) or C3. The mutation in this patient was identified in exon 12 of CFB and changes a lysine at amino acid position 533 to an arginine (c.1598A>G p.Lys533Arg). The two other mutations previously reported in CFB associated with aHUS are c.858C>G, p.F286L in exon 6 and c.967A>Gp.K323E in exon 7.

Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Aller AE, Abarrategui GC, López-Trascasa M, Sánchez-Corral P, Morgan P, Rodrıguez de Cordoba S (2007) Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci USA 104:240–245CrossRefPubMed

Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S, Skerka C, Marziliano N, Remuzzi G, Noris M (2001) The molecular basis of familial hemolytic uremic syndrome: mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol 12:297–307PubMed

Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM, Turnpenny P, Goodship JA (1998) Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int 53:836–844CrossRefPubMed

Fremeaux-Bacchi V, Moulton EA, Kavanagh D, Dragon-Durey MA, Blouin J, Caudy A, Arzouk N, Cleper R, Francois M, Guest G, Pourrat J, Seligman R, Fridman WH, Loirat C, Atkinson JP (2006) Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome. J Am Soc Nephrol 17:2017–2025CrossRefPubMed

Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Muslumanoglu MH, Kavukcu S, Filler G, Pirson Y, Wen LS, Atkinson JP, Goodship TH (2003) Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci USA 100:12966–12971CrossRefPubMed

Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, Vigneau C, Kuypers D, Boudailliez B, Loirat C, Rondeau E, Fridman WH (2004) Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet 41:e84CrossRefPubMed

Kavanagh D, Richards A, Noris M, Hauhart R, Liszewski MK, Karpman D, Goodship JA, Fremeaux-Bacchi V, Remuzzi G, Goodship TH, Atkinson JP (2008) Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. Mol Immunol 45:95–105CrossRefPubMed

Dragon-Durey MA, Loirat C, Cloarec S, Macher MA, Blouin J, Nivet H, Weiss L, Fridman WH, Fremeaux-Bacchi V (2005) Antifactor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol 16:555–563CrossRefPubMed

Jozsi M, Licht C, Strobel S, Zipfel SL, Richter H, Heinen S, Zipfel PF, Skerka C (2008) Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood 111:1512–1514CrossRefPubMed

10.

Fremeaux-Bacchi V, Goodship T, Regnier C, Dragon-Durey M, Janssen B, Atkinson J (2007) Mutations in complement C3 predispose to development of atypical haemolytic uraemic syndrome. Mol Immunol 44:3923CrossRef

11.

Moake JL (2002) Thrombotic microangiopathies. N Engl J Med 347:589–600CrossRefPubMed

12.

Hourcade D, Mitchell L, Oglesby T (1998) A conserved element in the serine protease domain of complement factor B. J Biol Chem 273:25996–26000CrossRefPubMed

13.

Ponnuraj I, Xu Y, Macon K, Moore D, Volanakis JE, Narayana SV (2004) Structural analysis of engineered bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. Mol Cell 14:17–28CrossRefPubMed

14.

Torreiraa E, Tortajadaa A, Montes TA, de Cordoba SR, Llorcaa O (2009) 3D structure of the C3bB complex provides insights into the activation and regulation of the complement alternative pathway convertase. Proc Natl Acad Sci USA106:882–887

15.

Stratton JD, Warwicker P (2002) Successful treatment of factor H related haemolytic uraemic syndrome. Nephrol Dial Transplant 17:684–685CrossRefPubMed

16.

Davin JC, Olie KH, Verlaak R, Horuz F, Florquin S, Weening JJ, Groothoff JW, Strain L, Goodship TH (2006) Complement factor H-associated atypical hemolytic uremic syndrome in monozygotic twins: concordant presentation, discordant response to treatment. Am J Kidney Dis 47:e27–e30CrossRefPubMed

17.

Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, Boudailliez B, Bouissou F, Deschenes G, Gie S, Tsimaratos M, Fischbach M, Morin D, Nivet H, Alberti C, Loirat C (2007) Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 18:2392–2400CrossRefPubMed

18.

Pickering MC, Cook HT (2008) Translational mini-review series on complement factor H: renal diseases associated with complement factor H: novel insights from humans and animals. Clin Exp Immunol 151:210–230PubMedCrossRef

19.

Saland JM, Ruggenenti P, Remuzzi G, the Consensus Study Group (2009) Liver-Kidney transplantation to cure atypical hemolytic uremic syndrome. J Am Soc Nephrol 20:940–949CrossRefPubMed

20.

Pickering MC, Warren J, Rose KL, Carlucci F, Wang Y, Walport MJ, Cook HT, Botto M (2006) Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice. Proc Natl Acad Sci USA 103:9649–9654CrossRefPubMed

21.

Loirat C, Fremeaux-Bacchi V (2008) Hemolytic uremic syndrome recurrence after renal transplantation. Pediatr Transplant 12:619–629CrossRefPubMed

22.

Fremeaux-Bacchi V, Arzouk N, Ferlicot S, Charpentier B, Snanoudj R, Durrbach A (2007) Recurrence of HUS due to CD46/MCP mutation after renal transplantation: a role for endothelial microchimerism. Am J Transplant 7:2047–2051CrossRefPubMed

23.

Saland JM, Emre SH, Shneider BL, Benchimol C, Ames S, Bromberg JS, Remuzzi G, Strain L, Goodship TH (2006) Favorable long-term outcome after liver-kidney transplant for recurrent hemolytic uremic syndrome associated with a factor H mutation. Am J Transplant 6:1948–1952CrossRefPubMed

24.

Jalanko H, Peltonen S, Koskinen A, Puntila J, Isoniemi H, Holmberg C, Pinomaki A, Armstrong E, Koivusalo A, Tukiainen E, Makisalo H, Saland J, Remuzzi G, de Cordoba S, Lassila R, Meri S, Jokiranta TS (2008) Successful liver–kidney transplantation in two children with aHUS caused by a mutation in complement factor H. Am J Transplant 8:216–221PubMed

25.

Loirat C, Noris M, Fremeaux-Bacchi V (2008) Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 23:1957–1972CrossRefPubMed

Title: A novel mutation in the Complement Factor B gene (CFB) and atypical hemolytic uremic syndrome
Authors: Hanan Tawadrous
Tara Maga
Josefina Sharma
Juan Kupferman
Richard J. H. Smith
Morris Schoeneman
Publication date: 01-05-2010
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 5/2010
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-009-1415-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A novel mutation in the Complement Factor B gene (CFB) and atypical hemolytic uremic syndrome

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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