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.