title: Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation.
abstract: Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the complement system and has a significantly poor prognosis. The clinical phenotypes of 12 patients in nine families with aHUS with familial or recurrent onset and ADAMTS13 activity of ≥20 % treated at the Mie University Hospital were examined. In seven of the patients, the first episode of aHUS occurred during childhood and ten patients experienced a relapse. All patients had renal dysfunction and three had been treated with hemodialysis. Seven patients experienced probable triggering events including common cold, influenza, bacterial infection and/or vaccination for influenza. All patients had entered remission, and renal function was improved in 11 patients. DNA sequencing of six candidate genes, identified a C3 p.I1157T missense mutation in all eight patients in six families examined and this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H, p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining seven missense mutations were likely neutral. In conclusion, the clinical phenotypes of aHUS are various, and there are often trigger factors. The C3 p.I1157T mutation was identified as the causative mutation for aHUS in all patients examined, and may be geographically concentrated in or around the Mie prefecture in central Japan.
authors.affiliation: Blood Transfusion Service, Mie University Hospital, Tsu, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Xinping
authors.initials: X
authors.lastname: Fan
authors.forename: Eiji
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Keishirou
authors.initials: K
authors.lastname: Amano
authors.forename: Hidemi
authors.initials: H
authors.lastname: Toyoda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
authors.forename: Kohshi
authors.initials: K
authors.lastname: Ohishi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Ikejiri
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D006435:Renal Dialysis; D018180:Thrombomodulin / Q000235:genetics; D055815:Young Adult
chemical_list: C038245:C3 protein, human; D003176:Complement C3; C546931:THBD protein, human; D018180:Thrombomodulin; D017242:Complement Factor H