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Diamond-Blackfan anemia (DBA)

Written1999-05Hope H. Punnett
Harvard Medical School, Children's Hospital Boston, 300 Longwood Ave. Boston, MA 02115, USA
Updated2007-02Hanna T. Gazda
Harvard Medical School, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA

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Identity

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

Clinics

Note
  • 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
    Protein
    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.
    Mutations
    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
    DNA/RNA
    Description ribosomal protein S24
    Mutations
    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%).

    Bibliography

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    Citation

    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 : http://AtlasGeneticsOncology.org/Tumors/DiamondBlackfanID10040.html
    History of this paper:
    Punnett, HH. Diamond-Blackfan anemia (DBA). Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):164-165.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37547/05-1999-DiamondBlackfanID10040.pdf

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