title: Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia.
abstract: 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 approximately 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.
authors.affiliation: Department of Cell Physiology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. racm@centrum.cz
authors.forename: Radek
authors.initials: R
authors.lastname: Cmejla
authors.forename: Jana
authors.initials: J
authors.lastname: Cmejlova
authors.forename: Helena
authors.initials: H
authors.lastname: Handrkova
authors.forename: Jiri
authors.initials: J
authors.lastname: Petrak
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pospisilova
mesh_terms: D000328:Adult; D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D018387:Codon, Initiator; D006801:Humans; D008297:Male; D009154:Mutation; D012269:Ribosomal Proteins / Q000235:genetics*; D054679:Ribosome Subunits, Small / Q000235:genetics
chemical_list: D018387:Codon, Initiator; D012269:Ribosomal Proteins; C037084:ribosomal protein S17