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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. 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.

journal_name

Haematologica

journal_title

Haematologica

authors

Konno Y,Toki T,Tandai S,Xu G,Wang R,Terui K,Ohga S,Hara T,Hama A,Kojima S,Hasegawa D,Kosaka Y,Yanagisawa R,Koike K,Kanai R,Imai T,Hongo T,Park MJ,Sugita K,Ito E

doi

10.3324/haematol.2009.020826

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

1293-9

issue

8

eissn

0390-6078

issn

1592-8721

pii

haematol.2009.020826

journal_volume

95

pub_type

杂志文章,多中心研究

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