A complement factor B mutation in a large kindred with atypical hemolytic uremic syndrome.

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. 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.

Citation

Michinori Funato, Osamu Uemura, Katsumi Ushijima, Hidenori Ohnishi, Kenji Orii, Zenichiro Kato, Satoshi Yamakawa, Takuhito Nagai, Osamu Ohara, Hideo Kaneko, Naomi Kondo. A complement factor B mutation in a large kindred with atypical hemolytic uremic syndrome. Journal of clinical immunology. 2014 Aug;34(6):691-5

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PMID: 24906628

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