Details of Disease

Disease Name

Diamond-Blackfan anemia

BDS; aregenerative anemia chronic congenital; anaemia congenital erythroid hypoplastic; Blackfan Diamond syndrome; aregenerative anaemia chronic congenital; Red cell aplasia, pure hereditary; anaemia Diamond Blackfan type; anemia congenital erythroid hypoplastic; anemia Diamond Blackfan type; Diamond-Blackfan anemia; Blackfan-Diamond anaemia; Blackfan-Diamond anemia; Aase-Smith II syndrome; DBA; inherited erythroblastopenia; Diamond Blackfan Anemia; congenital hypoplastic anaemia; congenital pure red cell aplasia; Blackfan - Diamond syndrome; congenital hypoplastic anemia; congenital hypoplastic anemia, Blackfan-Diamond type; erythrogenesis imperfecta; congenital PRCA; Aase syndrome; chronic constitutional pure red cell anemia; chronic constitutional pure red cell anaemia

Definition

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.

Disease Hierarchy

DISO9M7N: Inherited aplastic anemia

DIST91OT: Pure red-cell aplasia

DISI2SNW: Diamond-Blackfan anemia

Disease Identifiers

MONDO ID

MONDO_0015253

MESH ID

D029503

UMLS CUI

C1260899

MedGen ID

266045

HPO ID

HP:0004810

Orphanet ID

124

SNOMED CT ID

88854002

General Information of Disease (ID: DISI2SNW)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 10 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Betamethasone	DMAHJEF	Approved	Small molecular drug	[1]
Cortisone Acetate	DMG8K57	Approved	Small molecular drug	[2]
Dexamethasone	DMMWZET	Approved	Small molecular drug	[3]
Dromostanolone	DMF2JDG	Approved	Small molecular drug	[4]
Hydrocortisone	DMGEMB7	Approved	Small molecular drug	[5]
Methylprednisolone	DM4BDON	Approved	Small molecular drug	[6]
Oxymetholone	DMFXUT8	Approved	Small molecular drug	[7]
Prednisolone	DMQ8FR2	Approved	Small molecular drug	[8]
Prednisone	DM2HG4X	Approved	Small molecular drug	[9]
Triamcinolone	DM98IXF	Approved	Small molecular drug	[10]
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⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EPO	TTQG4NR	Limited	Biomarker	[11]
RPL15	TTQRVC9	Supportive	Autosomal dominant	[12]
ADA	TTLP57V	Strong	Altered Expression	[13]
CD34	TTZAVYN	Strong	Biomarker	[14]
CDA	TTQ12RK	Strong	Genetic Variation	[15]
PRMT3	TTL4XSQ	Strong	Genetic Variation	[16]
RPL15	TTQRVC9	Strong	Biomarker	[17]
TEC	TT1ZV49	Strong	Biomarker	[18]
THPO	TTCG5PE	Strong	Altered Expression	[19]
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⏷ Show the Full List of 9 DTT(s)

This Disease Is Related to 45 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
RPL13	OTFKNTD6	Limited	Biomarker	[20]
RPL19	OT33LM66	Limited	Biomarker	[21]
RPL8	OTHMZ1R9	Limited	Autosomal dominant	[22]
ADA2	OTGCV24S	Supportive	Autosomal dominant	[23]
GATA1	OTX1R7O1	Supportive	Autosomal dominant	[24]
RPL11	OT3VZ6OE	Supportive	Autosomal dominant	[12]
RPL15	OT7Y42LL	Supportive	Autosomal dominant	[12]
RPL18	OTJCH62J	Supportive	Autosomal dominant	[25]
RPL26	OTFNRC27	Supportive	Autosomal dominant	[12]
RPL35	OTFZX52Q	Supportive	Autosomal dominant	[25]
RPL35A	OTDDJUWF	Supportive	Autosomal dominant	[12]
RPL5	OTM8EBRI	Supportive	Autosomal dominant	[12]
RPS15A	OT0BUA12	Supportive	Autosomal dominant	[26]
RPS17	OTWHZ2JQ	Supportive	Autosomal dominant	[12]
RPS20	OTI8052R	Supportive	Autosomal dominant	[27]
RPS26	OTBYTA6A	Supportive	Autosomal dominant	[12]
RPS28	OT12IES1	Supportive	Autosomal dominant	[28]
RPS29	OTCC1872	Supportive	Autosomal dominant	[29]
RPS7	OTIK25WI	Supportive	Autosomal dominant	[12]
TSR2	OTSIWJQJ	Supportive	Autosomal dominant	[28]
DDX21	OTV73GMZ	moderate	Genetic Variation	[30]
KLF1	OT1FK08U	moderate	Altered Expression	[31]
BAMBI	OTCEJ8W5	Strong	Biomarker	[32]
CSDE1	OT15D7GH	Strong	Altered Expression	[33]
DIPK1A	OTWS5V2I	Strong	CausalMutation	[21]
GABARAPL1	OT4U7SBG	Strong	Biomarker	[34]
GABARAPL2	OTS7YVHF	Strong	Biomarker	[34]
IL3	OT0CQ35N	Strong	Altered Expression	[35]
LEFTY1	OT51HVC4	Strong	Biomarker	[36]
MTUS1	OTBPALMU	Strong	Biomarker	[37]
RPL23	OTXI1YLM	Strong	Biomarker	[17]
RPL27	OTWEOUTX	Strong	Biomarker	[17]
RPL31	OTV9E1OE	Strong	Biomarker	[17]
RPL36	OT9R9LWG	Strong	Biomarker	[17]
RPL41	OTFW5IFO	Strong	Genetic Variation	[38]
RPL9	OTKE01O8	Strong	Genetic Variation	[39]
RPS14	OTB90KV5	Strong	Genetic Variation	[40]
RPS15	OT0WYZYG	Strong	Biomarker	[17]
RPS21	OT6P58W6	Strong	Biomarker	[41]
RPS27	OTFXKY7P	Strong	Biomarker	[17]
RPS27A	OTIIGGZ2	Strong	Biomarker	[42]
SBDS	OTHDCCIB	Strong	Genetic Variation	[43]
RPS10	OTE3VSAH	Definitive	Autosomal dominant	[44]
RPS19	OTBKGP48	Definitive	Autosomal dominant	[44]
RPS24	OTSNKIL5	Definitive	Autosomal dominant	[44]
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⏷ Show the Full List of 45 DOT(s)

References

1	Betamethasone FDA Label
2	Cortisone acetate FDA Label
3	Dexamethasone FDA Label
4	Dromostanolone FDA Label
5	Hydrocortisone FDA Label
6	Methylprednisolone FDA Label
7	Oxymetholone FDA Label
8	Prednisolone FDA Label
9	Prednisone FDA Label
10	Triamcinolone FDA Label
11	Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation. Cell. 2017 Mar 9;168(6):1053-1064.e15. doi: 10.1016/j.cell.2017.02.026.
12	Diamond-Blackfan Anemia. 2009 Jun 25 [updated 2023 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
13	The role of the DNA damage response in zebrafish and cellular models of Diamond Blackfan anemia.Dis Model Mech. 2014 Jul;7(7):895-905. doi: 10.1242/dmm.015495. Epub 2014 May 8.
14	Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis.Blood. 2011 Aug 25;118(8):2296-304. doi: 10.1182/blood-2010-11-318543. Epub 2011 Apr 28.
15	Study of pathophysiology and molecular characterization of congenital anemia in India using targeted next-generation sequencing approach.Int J Hematol. 2019 Nov;110(5):618-626. doi: 10.1007/s12185-019-02716-9. Epub 2019 Aug 10.
16	Tyrosine 87 is vital for the activity of human protein arginine methyltransferase 3 (PRMT3).Biochim Biophys Acta. 2011 Feb;1814(2):277-82. doi: 10.1016/j.bbapap.2010.10.011. Epub 2010 Nov 5.
17	Germline Genetic Predisposition to Hematologic Malignancy.J Clin Oncol. 2017 Mar 20;35(9):1018-1028. doi: 10.1200/JCO.2016.70.8644. Epub 2017 Feb 13.
18	Familial transient erythroblastopenia of childhood is associated with the chromosome 19q13.2 region but not caused by mutations in coding sequences of the ribosomal protein S19 (RPS19) gene.Br J Haematol. 2002 Oct;119(1):261-4. doi: 10.1046/j.1365-2141.2002.03776.x.
19	Elevated thrombopoietin levels and alterations in the sequence of its receptor, c-Mpl, in patients with Diamond-Blackfan anemia.Haematologica. 2004 Nov;89(11):1391-2.
20	Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia. Br J Haematol. 2015 Mar;168(6):854-64. doi: 10.1111/bjh.13229. Epub 2014 Nov 25.
21	Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Br J Haematol. 2013 Aug;162(4):530-6. doi: 10.1111/bjh.12397. Epub 2013 May 30.
22	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
23	The Genetic Landscape of Diamond-Blackfan Anemia. Am J Hum Genet. 2018 Dec 6;103(6):930-947. doi: 10.1016/j.ajhg.2018.10.027. Epub 2018 Nov 29.
24	Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med. 2014 Jul;20(7):748-53. doi: 10.1038/nm.3557. Epub 2014 Jun 22.
25	Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation. J Med Genet. 2017 Jun;54(6):417-425. doi: 10.1136/jmedgenet-2016-104346. Epub 2017 Mar 9.
26	Exome sequencing identified RPS15A as a novel causative gene for Diamond-Blackfan anemia. Haematologica. 2017 Mar;102(3):e93-e96. doi: 10.3324/haematol.2016.153932. Epub 2016 Dec 1.
27	Expansion of germline RPS20 mutation phenotype to include Diamond-Blackfan anemia. Hum Mutat. 2020 Nov;41(11):1918-1930. doi: 10.1002/humu.24092. Epub 2020 Aug 30.
28	Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am J Med Genet A. 2014 Sep;164A(9):2240-9. doi: 10.1002/ajmg.a.36633. Epub 2014 Jun 18.
29	Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood. 2014 Jul 3;124(1):24-32. doi: 10.1182/blood-2013-11-540278. Epub 2014 May 14.
30	Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.Nature. 2018 Feb 1;554(7690):112-117. doi: 10.1038/nature25449. Epub 2018 Jan 24.
31	Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and erythroid progenitor in 5q- syndrome and in Diamond-Blackfan anemia.Ann Hematol. 2013 Jan;92(1):11-8. doi: 10.1007/s00277-012-1568-1. Epub 2012 Sep 11.
32	Dysregulation of the Transforming Growth Factor Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia.PLoS One. 2015 Aug 10;10(8):e0134878. doi: 10.1371/journal.pone.0134878. eCollection 2015.
33	Csde1 binds transcripts involved in protein homeostasis and controls their expression in an erythroid cell line.Sci Rep. 2018 Feb 8;8(1):2628. doi: 10.1038/s41598-018-20518-7.
34	MicroRNA expression profiling of dibenzalacetone (DBA) treated intracellular amastigotes of Leishmania donovani.Exp Parasitol. 2018 Oct;193:5-19. doi: 10.1016/j.exppara.2018.07.018. Epub 2018 Aug 17.
35	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.Blood. 2005 Jun 15;105(12):4620-6. doi: 10.1182/blood-2004-08-3313. Epub 2005 Mar 8.
36	RAP-011 improves erythropoiesis in zebrafish model of Diamond-Blackfan anemia through antagonizing lefty1.Blood. 2015 Aug 13;126(7):880-90. doi: 10.1182/blood-2015-01-622522. Epub 2015 Jun 24.
37	Regulation of globin-heme balance in Diamond-Blackfan anemia by HSP70/GATA1.Blood. 2019 Mar 21;133(12):1358-1370. doi: 10.1182/blood-2018-09-875674. Epub 2019 Jan 30.
38	A Novel 12q13.2-q13.3 Microdeletion Syndrome With Combined Features of Diamond Blackfan Anemia, Pierre Robin Sequence and Klippel Feil Deformity.Front Genet. 2018 Nov 19;9:549. doi: 10.3389/fgene.2018.00549. eCollection 2018.
39	Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism.Nucleic Acids Res. 2020 Jan 24;48(2):770-787. doi: 10.1093/nar/gkz1042.
40	Diminutive somatic deletions in the 5q region lead to a phenotype atypical of classical 5q- syndrome.Blood. 2013 Oct 3;122(14):2487-90. doi: 10.1182/blood-2013-06-509935. Epub 2013 Aug 13.
41	Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia. Hum Mutat. 2012 Jul;33(7):1037-44. doi: 10.1002/humu.22081. Epub 2012 Apr 16.
42	Overexpression of RPS27a contributes to enhanced chemoresistance of CML cells to imatinib by the transactivated STAT3.Oncotarget. 2016 Apr 5;7(14):18638-50. doi: 10.18632/oncotarget.7888.
43	Do ribosomopathies explain some cases of common variable immunodeficiency?.Clin Exp Immunol. 2011 Jan;163(1):96-103. doi: 10.1111/j.1365-2249.2010.04280.x. Epub 2010 Nov 9.
44	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.