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Diamond-Blackfan anemia (DBA)

Written2007-02Hanna T. Gazda
Harvard Medical School, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA
This article is an update of :
1999-05Hope H. Punnett
Harvard Medical School, Children's Hospital Boston, 300 Longwood Ave. Boston, MA 02115, USA

(Note : for Links provided by Atlas : click)


Atlas_Id 10040
Genes implicated inRPL5   RPL11   RPL15   RPL26   RPL35A   RPS7   RPS10   RPS17   RPS19   RPS24   RPS26   RPS28   RPS29   TSR2  
Inheritance Genetic heterogeneity; majority of cases autosomal dominant, occasionally with variable expression (incomplete dominance) manifesting as mild anemia or only macrocytosis and/or elevated erythrocyte adenosine deaminase activity (eADA) in transmitting parent or in siblings; some cases apparently autosomal recessive, not linked to 19q


  • Chronic constitutional aregenerative anemia with absent or decreased red cell precursors in bone marrow.
  • Macrocytosis, elevated fetal hemoglobin and increased eADA.
  • Physical abnormalities in about 40% of DBA cases including craniofacial and thumb abnormalities, atrial or ventrucular septal defects, short stature, mild retardation, etc.
  • Hematologic malignancy : in 2.5% of all reported cases of DBA; primarily ANLL with no FAB preference but also ALL, Hodgkin's disease.
  • Solid tumors include carcinoma of liver, stomach, osteogenic sarcoma.
  • Age of malignancy onset from 2 to 43 years.
  • Disease-related and treatment-related factors, i.e., allosensitization and iron overload, contribute to malignancy.
  • Treatment Corticosteroids, transfusion, bone marrow transplant.
    Evolution Some patients enter remission, with or without corticosteroid therapy.
    Prognosis Median survival: 38 years

    Genes involved and Proteins

    Gene NameRPS19 (ribosomal protein S19)
    Location 19q13.2
    Description Ribosomal protein S19; ribosomal proteins are a major component of cellular proteins. In general their function(s), aside from being part of the ribosome, are unknown. However, RPS19 protein was shown to be essential for 18S rRNA maturation and 40S subunit synthesis. Haplo-insufficiency of the protein encoded by the mutated gene is a likely mechanism underlying the pathogenesis of DBA.
    Germinal 62 different heterozygous mutations in RPS19 were identified and reported in 113 of the 457 (about 25%) DBA probands. They were non-sense, frameshift, splice site and missense mutations. Several patients had disease-associated chromosomal abnormalities in DBA region, including t(X;19), t(8;19), and 19q microdeletions.

    Gene NameRPS24 (ribosomal protein S24)
    Location 10q22.3
    Description ribosomal protein S24
    Germinal Three heterozygous mutations in RPS24 (two nonsense and one splice site mutations causing premature termination codons and skipped exon, respectively) were identified among 185 RPS19-negative DBA probands (about 2%).


    Impaired ribosome biogenesis in Diamond-Blackfan anemia.
    Choesmel V, Bacqueville D, Rouquette J, Noaillac-Depeyre J, Fribourg S, Crétien A, Leblanc T, Tchernia G, Da Costa L, Gleizes PE
    Blood. 2007 ; 109 (3) : 1275-1283.
    PMID 17053056
    Translational efficiency in patients with Diamond-Blackfan anemia.
    Cmejlova J, Dolezalova L, Pospisilova D, Petrtylova K, Petrak J, Cmejla R
    Haematologica. 2006 ; 91 (11) : 1456-1464.
    PMID 17082006
    Ribosomal protein S19 expression during erythroid differentiation.
    Da Costa L, Narla G, Willig TN, Peters LL, Parra M, Fixler J, Tchernia G, Mohandas N
    Blood. 2003 ; 101 (1) : 318-324.
    PMID 12393682
    The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia.
    Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N
    Nature genetics. 1999 ; 21 (2) : 169-175.
    PMID 9988267
    An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray.
    Ebert BL, Lee MM, Pretz JL, Subramanian A, Mak R, Golub TR, Sieff CA
    Blood. 2005 ; 105 (12) : 4620-4626.
    PMID 15755903
    High-risk pregnancies in Diamond-Blackfan anemia: a survey of 64 pregnancies from the French and German registries.
    Faivre L, Meerpohl J, Da Costa L, Marie I, Nouvel C, Gnekow A, Bender-Götze C, Bauters F, Coiffier B, Peaud PY, Rispal P, Berrebi A, Berger C, Flesch M, Sagot P, Varet B, Niemeyer C, Tchernia G, Leblanc T
    Haematologica. 2006 ; 91 (4) : 530-533.
    PMID 16537118
    Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits.
    Flygare J, Aspesi A, Bailey JC, Miyake K, Caffrey JM, Karlsson S, Ellis SR
    Blood. 2007 ; 109 (3) : 980-986.
    PMID 16990592
    Diamond-Blackfan anemia: erythropoiesis lost in translation.
    Flygare J, Karlsson S
    Blood. 2007 ; 109 (8) : 3152-3154.
    PMID 17164339
    Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia.
    Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, Vlachos A, Atsidaftos E, Ball SE, Orfali KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan DG, Beggs AH, Sieff CA
    American journal of human genetics. 2006 ; 79 (6) : 1110-1118.
    PMID 17186470
    Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia.
    Gazda HT, Kho AT, Sanoudou D, Zaucha JM, Kohane IS, Sieff CA, Beggs AH
    Stem cells (Dayton, Ohio). 2006 ; 24 (9) : 2034-2044.
    PMID 16741228
    RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations.
    Gazda HT, Zhong R, Long L, Niewiadomska E, Lipton JM, Ploszynska A, Zaucha JM, Vlachos A, Atsidaftos E, Viskochil DH, Niemeyer CM, Meerpohl JJ, Rokicka-Milewska R, Pospisilova D, Wiktor-Jedrzejczak W, Nathan DG, Beggs AH, Sieff CA
    British journal of haematology. 2004 ; 127 (1) : 105-113.
    PMID 15384984
    Identification of microdeletions spanning the Diamond-Blackfan anemia locus on 19q13 and evidence for genetic heterogeneity.
    Gustavsson P, Garelli E, Draptchinskaia N, Ball S, Willig TN, Tentler D, Dianzani I, Punnett HH, Shafer FE, Cario H, Ramenghi U, Glomstein A, Pfeiffer RA, Goringe A, Olivieri NF, Smibert E, Tchernia G, Elinder G, Dahl N
    American journal of human genetics. 1998 ; 63 (5) : 1388-1395.
    PMID 9792865
    Diamond-Blackfan anemia. Natural history and sequelae of treatment.
    Janov AJ, Leong T, Nathan DG, Guinan EC
    Medicine. 1996 ; 75 (2) : 77-78.
    PMID 8606629
    Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect.
    Ohene-Abuakwa Y, Orfali KA, Marius C, Ball SE
    Blood. 2005 ; 105 (2) : 838-846.
    PMID 15238419
    Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity.
    Orfali KA, Ohene-Abuakwa Y, Ball SE
    British journal of haematology. 2004 ; 125 (2) : 243-252.
    PMID 15059149
    Analysis of the ribosomal protein S19 interactome.
    Orrù S, Aspesi A, Armiraglio M, Caterino M, Loreni F, Ruoppolo M, Santoro C, Dianzani I
    Molecular & cellular proteomics : MCP. 2007 ; 6 (3) : 382-393.
    PMID 17151020
    The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia.
    Vlachos A, Klein GW, Lipton JM
    Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 2001 ; 23 (6) : 377-382.
    PMID 11563775
    Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression.
    Willig TN, Draptchinskaia N, Dianzani I, Ball S, Niemeyer C, Ramenghi U, Orfali K, Gustavsson P, Garelli E, Brusco A, Tiemann C, Pérignon JL, Bouchier C, Cicchiello L, Dahl N, Mohandas N, Tchernia G
    Blood. 1999 ; 94 (12) : 4294-4306.
    PMID 10590074
    Diamond-Blackfan anemia and malignancy. A case report and a review of the literature.
    van Dijken PJ, Verwijs W
    Cancer. 1995 ; 76 (3) : 517-520.
    PMID 8625135


    This paper should be referenced as such :
    Gazda, HT
    Diamond-Blackfan anemia (DBA)
    Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):256-257.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Punnett, HH. Diamond-Blackfan anemia (DBA). Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):164-165.

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes GATA1

    External links

    OrphanetBlackfan-Diamond anemia
    Other databaseDiamond-Blackfan anemia (GARD)
    Genes implicated inRPL5   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPL11   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPL15   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPL26   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPL35A   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS7   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS10   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS17   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS19   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS24   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS26   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS28   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inRPS29   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inTSR2   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

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