Diamond-Blackfan anemia (DBA)

2007-02-01   Hanna T. Gazda 

Harvard Medical School, Childrens Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA



Diamond-Blackfan anemia (DBA)


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


105650 , 205900 , 300946 , 606129 , 606164 , 610629 , 612527 , 612528 , 612561 , 612562 , 612563 , 613308 , 613309 , 614900 , 615550 , 615909




124 Blackfan-Diamond anemia





  • 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, Hodgkins 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.


    Some patients enter remission, with or without corticosteroid therapy.


    Median survival: 38 years

    Genes involved and Proteins


    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.


    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.


    ribosomal protein S24


    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%).


    Pubmed IDLast YearTitleAuthors
    170530562007Impaired ribosome biogenesis in Diamond-Blackfan anemia.Choesmel V et al
    170820062006Translational efficiency in patients with Diamond-Blackfan anemia.Cmejlova J et al
    123936822003Ribosomal protein S19 expression during erythroid differentiation.Da Costa L et al
    99882671999The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia.Draptchinskaia N et al
    157559032005An 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 et al
    165371182006High-risk pregnancies in Diamond-Blackfan anemia: a survey of 64 pregnancies from the French and German registries.Faivre L et al
    169905922007Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits.Flygare J et al
    171643392007Diamond-Blackfan anemia: erythropoiesis lost in translation.Flygare J et al
    171864702006Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia.Gazda HT et al
    167412282006Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia.Gazda HT et al
    153849842004RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations.Gazda HT et al
    97928651998Identification of microdeletions spanning the Diamond-Blackfan anemia locus on 19q13 and evidence for genetic heterogeneity.Gustavsson P et al
    86066291996Diamond-Blackfan anemia. Natural history and sequelae of treatment.Janov AJ et al
    152384192005Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect.Ohene-Abuakwa Y et al
    150591492004Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity.Orfali KA et al
    171510202007Analysis of the ribosomal protein S19 interactome.Orrù S et al
    115637752001The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia.Vlachos A et al
    105900741999Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression.Willig TN et al
    86251351995Diamond-Blackfan anemia and malignancy. A case report and a review of the literature.van Dijken PJ et al