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.
DESIGN AND 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.