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Erschienen in: Journal of Clinical Immunology 6/2014

01.08.2014 | Brief Communication

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

verfasst von: Michinori Funato, Osamu Uemura, Katsumi Ushijima, Hidenori Ohnishi, Kenji Orii, Zenichiro Kato, Satoshi Yamakawa, Takuhito Nagai, Osamu Ohara, Hideo Kaneko, Naomi Kondo

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2014

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Abstract

Purpose

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.

Conclusions

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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Metadaten
Titel
A Complement Factor B Mutation in a Large Kindred with Atypical Hemolytic Uremic Syndrome
verfasst von
Michinori Funato
Osamu Uemura
Katsumi Ushijima
Hidenori Ohnishi
Kenji Orii
Zenichiro Kato
Satoshi Yamakawa
Takuhito Nagai
Osamu Ohara
Hideo Kaneko
Naomi Kondo
Publikationsdatum
01.08.2014
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 6/2014
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-014-0058-8

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