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A Complement Factor B Mutation in a Large Kindred with Atypical Hemolytic Uremic Syndrome

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Gain-of-function mutations in complement factor B (CFB) were recently identified in patients with atypical hemolytic uremic syndrome (aHUS), but are extremely rare. Our purpose is to describe a large kindred with aHUS associated with a CFB mutation and to further understand CFB-mutated aHUS patients.

Methods and Results

We report a large kindred in which 3 members had aHUS. This kindred revealed that 9 of 12 members, including 2 affected patients, had persistent activation of the alternative pathway with low complement component 3 and that those 9 members showed a CFB mutation (c.1050G > C, p.Lys350Asn) in exon 8. This missense mutation was heterozygous in 8 of them and homozygous in only one. From structural studies, this mutation is shown to be located in close proximity to the Mg2-binding site within a von Willebrand factor type A domain of CFB, resulting in a gain-of-function effect of CFB and predisposition to aHUS. At present, 2 of the 3 members with aHUS have maintained normal renal function for a long-term period.


This kindred illustrates that a CFB mutation (c.1050G > C, p.Lys350Asn) can result in aHUS. In the future, phenotype-genotype correlations and outcome in CFB-mutated aHUS patients need to be further investigated by accumulation of a number of cases.

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Fig. 1



Atypical hemolytic uremic syndrome


Complement factor H


Complement factor I


Membrane cofactor protein


Complement factor B


Complement component 3




von Willebrand factor type A


Serine protease


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We thank Masanori Matsumoto, Yoko Yoshida, and Yoshihiro Fujimura (Nara Medical University, Kashihara, Japan) for ADAMTS13 activity assay and Nobuaki Takagi and Hiromu Mae (Hyogo college of Medicine, Nishinomiya, Japan) for anti-factor H antibody assay.

This work was supported in part by Health and Labor Sciences Research Grants of Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare.

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The authors declare that they have no conflict of interest.

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Correspondence to Michinori Funato.

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Funato, M., Uemura, O., Ushijima, K. et al. A Complement Factor B Mutation in a Large Kindred with Atypical Hemolytic Uremic Syndrome. J Clin Immunol 34, 691–695 (2014).

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