Diamond-Blackfan anemia (DBA)

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Diamond-Blackfan anemia (DBA)

Identity

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 Name RPS19

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 Name RPS24

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

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

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

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

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

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, Pˆ©rignon JL, Bouchier C, Cicchiello L, Dahl N, Mohandas N, Tchernia G

Blood. 1999 ; 94 (12) : 4294-4306.

PMID 10590074

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

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

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

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

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

Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia.

Flygare J, Kiefer T, Miyake K, Utsugisawa T, Hamaguchi I, Da Costa L, Richter J, Davey EJ, Matsson H, Dahl N, Wiznerowicz M, Trono D, Karlsson S

Blood. 2005 ; 105 (12) : 4627-4634.

PMID 15626736

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

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

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-Gˆtze 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

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

Analysis of the ribosomal protein S19 interactome.

Orrˆ¼ 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

Impaired ribosome biogenesis in Diamond-Blackfan anemia.

Choesmel V, Bacqueville D, Rouquette J, Noaillac-Depeyre J, Fribourg S, Crˆ©tien A, Leblanc T, Tchernia G, Da Costa L, Gleizes PE

Blood. 2007 ; 109 (3) : 1275-1283.

PMID 17053056

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

REVIEW articles automatic search in PubMed

Last year publications automatic search in PubMed

Contributor(s)

Written 05-1999 Hope H. Punnett

Harvard Medical School, Children's Hospital Boston, 300 Longwood Ave. Boston, MA 02115, USA

Updated 02-2007 Hanna T. Gazda

Citation

This paper should be referenced as such :
Punnett HH . Diamond-Blackfan anemia (DBA). Atlas Genet Cytogenet Oncol Haematol. May 1999 .
URL : http://AtlasGeneticsOncology.org/Genes/DiamondBlackfanID10040.html

Gazda HT . Diamond-Blackfan anemia (DBA). Atlas Genet Cytogenet Oncol Haematol. February 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/DiamondBlackfanID10040.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Sep 24 21:08:00 2008

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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

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.

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%).

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Written	05-1999	Hope H. Punnett
		Harvard Medical School, Children's Hospital Boston, 300 Longwood Ave. Boston, MA 02115, USA
Updated	02-2007	Hanna T. Gazda