title: Truncating ribosomal protein S19 mutations and variable clinical expression in Diamond-Blackfan anemia.
abstract: Diamond-Blackfan anemia (DBA) is a rare constitutional erythroblastopenia characterized by a specific defect in erythroid differentiation. Recently, mutations in the gene encoding ribosomal protein (RP) S19 were found in a subset of patients with the disease. To characterize further RPS19 mutations and to investigate genotype-phenotype relationships, we screened this gene for mutations in patients with DBA by direct sequencing and Southern-blot analysis. Four novel mutations were identified. A G120A nonsense mutation resulting in a stop at codon 33, a C302T nonsense mutation introducing a premature stop at codon 84, and a 327delG which results in a frame shift at codon 103. A fourth and more complex mutation (TT157-158AA, 160insCT) resulting in a Leu45Gln and a frame shift from codon 47 was found in three affected family members with variable phenotypes. The different clinical expression for identical mutations suggest the presence of other modulating factors for the disease. The mutations presented here further support the role of RPS19 in erythropoietic differentiation and proliferation.
authors.affiliation: Department of Genetics and Pathology, The Rudbeck Laboratory, University Children's Hospital, Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Matsson
authors.forename: J
authors.initials: J
authors.lastname: Klar
authors.forename: N
authors.initials: N
authors.lastname: Draptchinskaia
authors.forename: P
authors.initials: P
authors.lastname: Gustavsson
authors.forename: B
authors.initials: B
authors.lastname: Carlsson
authors.forename: D
authors.initials: D
authors.lastname: Bowers
authors.forename: E
authors.initials: E
authors.lastname: de Bont
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D004247:DNA