title: Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia.
abstract: BACKGROUND
  Diamond-Blackfan anemia is a rare, clinically heterogeneous, congenital red cell aplasia: 40% of patients have congenital abnormalities. Recent studies have shown that in western countries, the disease is associated with heterozygous mutations in the ribosomal protein (RP) genes in about 50% of patients. There have been no studies to determine the incidence of these mutations in Asian patients with Diamond-Blackfan anemia.
  
  
  METHODS
  We screened 49 Japanese patients with Diamond-Blackfan anemia (45 probands) for mutations in the six known genes associated with Diamond-Blackfan anemia: RPS19, RPS24, RPS17, RPL5, RPL11, and RPL35A. RPS14 was also examined due to its implied involvement in 5q- syndrome.
  
  
  RESULTS
  Mutations in RPS19, RPL5, RPL11 and RPS17 were identified in five, four, two and one of the probands, respectively. In total, 12 (27%) of the Japanese Diamond-Blackfan anemia patients had mutations in ribosomal protein genes. No mutations were detected in RPS14, RPS24 or RPL35A. All patients with RPS19 and RPL5 mutations had physical abnormalities. Remarkably, cleft palate was seen in two patients with RPL5 mutations, and thumb anomalies were seen in six patients with an RPS19 or RPL5 mutation. In contrast, a small-for-date phenotype was seen in five patients without an RPL5 mutation.
  
  
  CONCLUSIONS
  We observed a slightly lower frequency of mutations in the ribosomal protein genes in patients with Diamond-Blackfan anemia compared to the frequency reported in western countries. Genotype-phenotype data suggest an association between anomalies and RPS19 mutations, and a negative association between small-for-date phenotype and RPL5 mutations.
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine,5 Zaifucho, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Konno
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Toki
authors.forename: Satoru
authors.initials: S
authors.lastname: Tandai
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Runan
authors.initials: R
authors.lastname: Wang
authors.forename: Kiminori
authors.initials: K
authors.lastname: Terui
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.forename: Ryu
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
authors.forename: Rie
authors.initials: R
authors.lastname: Kanai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Imai
authors.forename: Teruaki
authors.initials: T
authors.lastname: Hongo
authors.forename: Myoung-Ja
authors.initials: MJ
authors.lastname: Park
authors.forename: Kanji
authors.initials: K
authors.lastname: Sugita
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D012269:Ribosomal Proteins / Q000235:genetics*; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D012269:Ribosomal Proteins; D013256:Steroids; C027624:ribosomal protein L11; C029742:ribosomal protein L5; C039747:ribosomal protein S14; C037084:ribosomal protein S17; C040343:ribosomal protein S19