Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia
Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia
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DOI：
10.1002/humu.20608
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发表时间：
2007-12-01
期刊：
影响因子：
3.9
通讯作者：
Pospisilova, Dagmar
中科院分区：
文献类型：
--
作者：
Cmejla, Radek;Cmejlova, Jana;Pospisilova, Dagmar
Diamond-Blackfan贫血（DBA）是一种先天性红细胞再生障碍性贫血，其特征为正常色素性大细胞性贫血，在其他正常细胞骨髓中选择性缺乏红细胞前体。在40%的DBA患者中，还存在各种身体异常。目前，有两个基因与DBA表型相关-核糖体蛋白（RP）S19在25%的DBA患者中突变，RPS 24在1.4%的DBA患者中突变。在这里，我们报告的另一个核糖体蛋白，RPS 17的突变的鉴定。该突变影响翻译起始起始密码子，将T变为G（c.2T > G），从而消除了RPS 17蛋白生物合成的天然起始。RNA分析显示突变的等位基因被表达，并且位于+158位的下一个下游起始密码子应该产生仅4个氨基酸的短肽（Met-Ser-Arg-Ile）。这种突变是从头开始的，因为所有健康的家庭成员都携带野生型等位基因。DBA患者核糖体小亚基第三RP突变的鉴定进一步支持了翻译受损可能是DBA发病机制的主要原因的理论。《Mutat》28（12），1178-1182，2007年。(c)2007 Wiley-Liss，Inc.
Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia characterized as a normochromic macrocytic anemia with a selective deficiency in red blood cell precursors in otherwise normocellular bone marrow. In 40% of DBA patients, various physical anomalies are also present. Currently two genes are associated with the DBA phenotype-the ribosomal protein (RP) S19 mutated in 25% of DBA patients and RPS24 mutated in similar to 1.4% of DBA patients. Here we report the identification of a mutation in yet another ribosomal protein, RPS17. The mutation affects the translation initiation start codon, changing T to G (c.2T > G), thus eliminating the natural start of RPS17 protein biosynthesis. RNA analysis revealed that the mutated allele was expressed, and the next downstream start codon located at position +158 should give rise to a short peptide of only four amino acids (Met-Ser-Arg-Ile). The mutation arose de novo, since all healthy family members carry the wild, type alleles. The identification of a mutation in the third RP of the small ribosomal subunit in DBA patients further supports the theory that impaired translation may be the main cause of DBA pathogenesis. Hum Mutat 28(12), 1178-1182, 2007. (c) 2007 Wiley-Liss, Inc.