title: Analysis of genetic and predisposing factors in Japanese patients with atypical hemolytic uremic syndrome.
abstract: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Approximately 10% of cases are classified as atypical due to the absence of Shiga toxin-producing bacteria as a trigger. Uncontrolled activation of the complement system plays a role in the pathogenesis of atypical HUS (aHUS). Although many genetic studies on aHUS have been published in recent years, only limited data has been gathered in Asian countries. We analyzed the genetic variants of 6 candidate genes and the gene deletion in complement factor H (CFH) and CFH-related genes, examined the prevalence of CFH autoantibodies and evaluated the genotype-phenotype relationship in 10 Japanese patients with aHUS. We identified 7 causative or potentially causative mutations in CFH (p.R1215Q), C3 (p.R425C, p.S562L, and p.I1157T), membrane cofactor protein (p.Y189D and p.A359V) and thrombomodulin (p.T500M) in 8 out of 10 patients. All 7 of the mutations were heterozygous and four of them were novel. Two patients carried CFH p.R1215Q and 3 other patients carried C3 p.I1157T. One patient had 2 causative mutations in different genes. One patient was a compound heterozygote of the 2 MCP mutations. The patients carrying mutations in CFH or C3 had a high frequency of relapse and a worse prognosis. One patient had CFH autoantibodies. The present study identified the cause of aHUS in 9 out of 10 Japanese patients. Since the phenotype-genotype correlation of aHUS has clinical significance in predicting renal recovery and transplant outcome, a comprehensively accurate assessment of molecular variation would be necessary for the proper management of aHUS patients in Japan.
authors: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan.
authors: Xinping
authors: X
authors: Fan
authors: Yoko
authors: Y
authors: Yoshida
authors: Shigenori
authors: S
authors: Honda
authors: Masanori
authors: M
authors: Matsumoto
authors: Yugo
authors: Y
authors: Sawada
authors: Motoshi
authors: M
authors: Hattori
authors: Shuichi
authors: S
authors: Hisanaga
authors: Ryosuke
authors: R
authors: Hiwa
authors: Fumihiko
authors: F
authors: Nakamura
authors: Maiko
authors: M
authors: Tomomori
authors: Shinichiro
authors: S
authors: Miyagawa
authors: Rika
authors: R
authors: Fujimaru
authors: Hiroshi
authors: H
authors: Yamada
authors: Toshihiro
authors: T
authors: Sawai
authors: Yuhachi
authors: Y
authors: Ikeda
authors: Naoyuki
authors: N
authors: Iwata
authors: Osamu
authors: O
authors: Uemura
authors: Eiji
authors: E
authors: Matsukuma
authors: Yoshiaki
authors: Y
authors: Aizawa
authors: Hiroshi
authors: H
authors: Harada
authors: Hideo
authors: H
authors: Wada
authors: Eiji
authors: E
authors: Ishikawa
authors: Akira
authors: A
authors: Ashida
authors: Masaomi
authors: M
authors: Nangaku
authors: Toshiyuki
authors: T
authors: Miyata
authors: Yoshihiro
authors: Y
authors: Fujimura
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D065766:Atypical Hemolytic Uremic Syndrome; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D055815:Young Adult