title: Ribosomal protein mutations in Korean patients with Diamond-Blackfan anemia.
abstract: Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer. DBA has been associated with mutations and deletions in the large and small ribosomal protein genes, and genetic aberrations have been detected in ∼50-60% of patients. In this study, nine Korean DBA patients were screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10, RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method. Mutations in RPS19, RPS26 and RPS17 were detected in four, two and one patient, respectively. Among the mutations detected in RPS19, two mutations were novel (c.26T>A, c.357-2A>G). For the mutation-negative cases, array-CGH analysis was performed to identify copy-number variations, and no deletions involving the known DBA gene regions were identified. The relative mRNA expression of RPS19 estimated using real-time quantitative PCR analysis revealed two- to fourfold reductions in RPS19 mRNA expression in three patients with RPS19 mutations, and p53 protein expression analysis by immunohistochemistry showed variable but significant nuclear staining in the DBA patients. In conclusion, heterozygous mutations in the known DBA genes RPS19, RPS26 and RPS17 were detected in seven out of nine Korean DBA patients. Among these patients, RPS19 was the most frequently mutated gene. In addition, decreased RPS19 mRNA expression and p53 overexpression were observed in the Korean DBA patients, which supports the hypothesis that haploinsufficiency and p53 hyperactivation represent a central pathway underlying the pathogenesis of DBA.
authors.affiliation: 1] Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea [2] Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Chae
authors.affiliation: 1] Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea [2] Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Joonhong
authors.initials: J
authors.lastname: Park
authors.affiliation: 1] Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea [2] Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seungok
authors.initials: S
authors.lastname: Lee
authors.affiliation: 1] Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea [2] Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.affiliation: 1] Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea [2] Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nack-Gyun
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dae Chul
authors.initials: DC
authors.lastname: Jeong
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jung Rok
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Geon
authors.initials: G
authors.lastname: Park
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056910:Republic of Korea; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53