title: A complement factor B mutation in a large kindred with atypical hemolytic uremic syndrome.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan, mfunato@me.com.
authors.forename: Michinori
authors.initials: M
authors.lastname: Funato
authors.forename: Osamu
authors.initials: O
authors.lastname: Uemura
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ushijima
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Orii
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamakawa
authors.forename: Takuhito
authors.initials: T
authors.lastname: Nagai
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Hideo
authors.initials: H
authors.lastname: Kaneko
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000328:Adult; D065766:Atypical Hemolytic Uremic Syndrome / Q000235:genetics*; D002648:Child; D003176:Complement C3 / Q000172:deficiency*; D011415:Complement Factor B / Q000235:genetics* / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011485:Protein Binding / Q000235:genetics; D055815:Young Adult
chemical_list: D003176:Complement C3; D016326:Extracellular Matrix Proteins; C460760:VWA1 protein, human; D011415:Complement Factor B