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Ribosomal protein S17 gene (RPS17) is mutated in Diamond‐Blackfan anemia
Author(s) -
Cmejla Radek,
Cmejlova Jana,
Handrkova Helena,
Petrak Jiri,
Pospisilova Dagmar
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20608
Subject(s) - diamond–blackfan anemia , biology , ribosomal protein , macrocytic anemia , mutation , genetics , gene , ribosomal rna , phenotype , microbiology and biotechnology , ribosome , rna , endocrinology , vitamin b12
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 ∼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. © 2007 Wiley‐Liss, Inc.