Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia
Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia
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DOI：
10.3324/haematol.2009.020826
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发表时间：
2010-08-01
期刊：
影响因子：
--
通讯作者：
Ito, Etsuro
中科院分区：
文献类型：
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作者：
Konno, Yuki;Toki, Tsutomu;Ito, Etsuro
背景Diamond-Blackfan贫血是一种罕见的、临床异质性的先天性红细胞再生障碍性贫血：40%的患者存在先天性异常。最近的研究表明，在西方国家，约50%的患者与核糖体蛋白（RP）基因的杂合突变有关。有没有研究，以确定这些突变的发病率在亚洲患者与Diamond-Blackfan anemia.Design and MethodsWe筛选49例日本患者与Diamond-Blackfan贫血（45 probands）的突变与Diamond-Blackfan贫血相关的6个已知基因：RPS 19，RPS 24，RPS 17，RPL 5，RPL 11，RPL 35 A。RPS 14也检查，由于其隐含的参与5 q-syndrome. ResultsRPS 19，RPL 5，RPL 11和RPS 17的突变被确定在5，4，2和1的先证者，分别。总共有12例（27%）日本Diamond-Blackfan贫血患者的核糖体蛋白基因发生突变。在RPS 14、RPS 24或RPL 35 A中未检测到突变。所有携带RPS 19和RPL 5突变的患者都有身体异常。值得注意的是，腭裂见于2例RPL 5突变患者，拇指畸形见于6例RPS 19或RPL 5突变患者。相比之下，一个小的最新的表型被认为是在5例没有RPL 5 mutation.ConclusionsWe观察到的核糖体蛋白基因的突变频率略低的钻石-布莱克凡贫血患者相比，在西方国家报道的频率。基因型-表型数据表明，异常和RPS 19突变之间的关联，以及小的最新表型和RPL 5突变之间的负相关。
BackgroundDiamond-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 MethodsWe 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.ResultsMutations 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.ConclusionsWe 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.