title: RPS19 mutations in patients with Diamond-Blackfan anemia.
abstract: Diamond-Blackfan anemia (DBA) is an inherited disease characterized by pure erythroid aplasia. Thirty percent (30%) of patients display malformations, especially of the hands, face, heart, and urogenital tract. DBA has an autosomal dominant pattern of inheritance. De novo mutations are common and familial cases display wide clinical heterogeneity. Twenty-five percent (25%) of patients carry a mutation in the ribosomal protein (RP) S19 gene, whereas mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5 are rare. These genes encode for structural proteins of the ribosome. A link between ribosomal functions and erythroid aplasia is apparent in DBA, but its etiology is not clear. Most authors agree that a defect in protein synthesis in a rapidly proliferating tissue, such as the erythroid bone marrow, may explain the defective erythropoiesis. A total of 77 RPS19 mutations have been described. Most are whole gene deletions, translocations, or truncating mutations (nonsense or frameshift), suggesting that haploinsufficiency is the basis of DBA pathology. A total of 22 missense mutations have also been described and several works have provided in vitro functional data for the mutant proteins. This review looks at the data on all these mutations, proposes a functional classification, and describes six new mutations. It is shown that patients with RPS19 mutations display a poorer response to steroids and a worse long-term prognosis compared to other DBA patients.
authors.affiliation: Department of Pediatric Sciences, Università di Torino, Torino, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Campagnoli
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
authors.forename: Marta
authors.initials: M
authors.lastname: Armiraglio
authors.forename: Paola
authors.initials: P
authors.lastname: Quarello
authors.forename: Emanuela
authors.initials: E
authors.lastname: Garelli
authors.forename: Adriana
authors.initials: A
authors.lastname: Carando
authors.forename: Federica
authors.initials: F
authors.lastname: Avondo
authors.forename: Elisa
authors.initials: E
authors.lastname: Pavesi
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fribourg
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Gleizes
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loreni
authors.forename: Irma
authors.initials: I
authors.lastname: Dianzani
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D012269:Ribosomal Proteins; C040343:ribosomal protein S19