Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia

被引:178
作者
Cmejla, Radek
Cmejlova, Jana
Handrkova, Helena
Petrak, Jiri
Pospisilova, Dagmar
机构
[1] Inst Hematol & Blood Transfus, Dept Cell Physiol, CR-12820 Prague, Czech Republic
[2] Palacky Univ, Dept Pediat, CR-77147 Olomouc, Czech Republic
关键词
ribosomal protein S17; RPS17; small ribosomal subunit; translation; Diamond-Blackfan anemia;
D O I
10.1002/humu.20608
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:1178 / 1182
页数:5
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