title: Clinical and genomic heterogeneity of Diamond Blackfan anemia in the Russian Federation.
abstract: BACKGROUND
  Diamond Blackfan anemia (DBA) is a genetically and clinically heterogeneous ribosomopathy and inherited bone marrow failure syndrome characterized by anemia, reticulocytopenia, and decreased erythroid precursors in the bone marrow with an increased risk of malignancy and, in approximately 50%, physical abnormalities.
  
  
  METHODS
  We retrospectively analyzed clinical data from 77 patients with DBA born in the Russian Federation from 1993 to 2014. In 74 families there was one clinically affected individual; in only three instances a multiplex family was identified. Genomic DNA from 57 DBA patients and their first-degree relatives was sequenced for mutations in RPS19, RPS10, RPS24, RPS26, RPS7, RPS17, RPL5, RPL11, RPL35a, and GATA1.
  
  
  RESULTS
  Severe anemia presented before 8 months of age in all 77 patients; before 2 months in 61 (78.2%); before 4 months in 71 (92.2%). Corticosteroid therapy was initiated after 1 year of age in the majority of patients. Most responded initially to steroids, while 5 responses were transient. Mutations in RP genes were detected in 35 of 57 patients studied: 15 in RPS19, 6 in RPL5, 3 in RPS7, 3 each in RPS10, RPS26, and RPL11 and 1 each in RPS24 and RPL35a; 24 of these mutations have not been previously reported. One patient had a balanced chromosomal translocation involving RPS19. No mutations in GATA1 were found.
  
  
  CONCLUSIONS
  In our cohort from an ethnically diverse population the distribution of mutations among RP genes was approximately the same as was reported by others, although within genotypes most of the mutations had not been previously reported.
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.|Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Smetanina
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Mersiyanova
authors.affiliation: Evrogen, Moscow, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Kurnikova
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Galina S
authors.initials: GS
authors.lastname: Ovsyannikova
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Lili A
authors.initials: LA
authors.lastname: Hachatryan
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Vlasta O
authors.initials: VO
authors.lastname: Bobrynina
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Maschan
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Novichkova
authors.affiliation: Hofstra North Shore-LIJ School of Medicine, Hempstead, New York.|Feinstein Institute for Medical Research (FIMR), Manhasset, New York.|Division of Hematology/Oncology and Stem Cell Transplantation, CCMC, New Hyde Park, New York.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Lipton
authors.affiliation: Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Maschan
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D029503:Anemia, Diamond-Blackfan / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D050982:GATA1 Transcription Factor / Q000172:deficiency / Q000235:genetics*; D018740:Genetic Heterogeneity; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics*; D012426:Russia / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D012269:Ribosomal Proteins
keywords: DBA; Diamond Blackfan anemia; ribosomal proteins