Details of Disease

Disease Name

Bloom syndrome

microcephaly, growth restriction, and increased sister chromatid exchange 1; MGRISCE1; growth deficiency, sun-sensitive, telangiectatic, hypo and hyperpigmented skin, predisposition to malignancy and chromosomal instability; BS; BLM; BLS; congenital telangiectatic erythema; BSyn; congenital telangiectatic erythema syndrome; Bloom-Torre-Machacek syndrome; Bloom syndrome

Definition

Bloom syndrome (BSyn) is a rare chromosomal breakage syndrome characterized by a marked genetic instability associated with pre- and postnatal growth retardation, facial sun-sensitive telangiectatic erythema, increased susceptibility to infections, and predisposition to cancer.

Disease Hierarchy

DISQCXZX: Disorder of development or morphogenesis

DISXNHQG: Microcephaly, growth restriction and increased sister chromatid exchange

DIS6SVEE: Syndromic disease

DISCPWH9: Autosomal recessive disease

DIS9XD9A: Hematologic disease

DISM5BB5: Chromosomal disorder

DISYJQB2: Hereditary photodermatosis

DISKXQ7J: Bloom syndrome

Disease Identifiers

MONDO ID

MONDO_0008876

MESH ID

D001816

UMLS CUI

C0005859

OMIM ID

210900

MedGen ID

2685

Orphanet ID

125

SNOMED CT ID

4434006

General Information of Disease (ID: DISKXQ7J)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRIP1	TTZV7LJ	moderate	Biomarker	[1]
CDA	TTQ12RK	moderate	Altered Expression	[2]
FANCF	TTNZKFJ	moderate	Biomarker	[3]
GP1BA	TTVB0Q9	moderate	Altered Expression	[4]
GPR17	TTMPART	moderate	Altered Expression	[5]
TOP2B	TT4NVEM	moderate	Biomarker	[6]
FES	TTLBY21	Strong	Biomarker	[7]
WRN	TT2H5WQ	Strong	Biomarker	[8]
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⏷ Show the Full List of 8 DTT(s)

This Disease Is Related to 40 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADAM15	OTZ7VLTP	moderate	Biomarker	[9]
ANKH	OTCN25R5	moderate	Biomarker	[10]
DDX1	OT3U8FD0	moderate	Biomarker	[11]
DMC1	OT1FHMW4	moderate	Biomarker	[12]
FANCB	OTMZTXB5	moderate	Genetic Variation	[13]
GYPB	OTESHUIX	moderate	Genetic Variation	[14]
GYPE	OTBHAG6A	moderate	Genetic Variation	[14]
KRT10	OTSVRD3Q	moderate	Biomarker	[15]
MS4A12	OTUCF3GW	moderate	Genetic Variation	[16]
NREP	OT2AZPKK	moderate	Altered Expression	[17]
PITX3	OTE2KT8P	moderate	Altered Expression	[18]
POLD4	OTG578YH	moderate	Altered Expression	[19]
RAD51D	OTKOU5XN	moderate	Biomarker	[20]
RAD54L	OTEGMAKG	moderate	Genetic Variation	[21]
RIF1	OTPE49OE	moderate	Biomarker	[11]
RMI2	OTA0HP4S	moderate	Biomarker	[22]
SLX4	OTF6236I	moderate	Biomarker	[23]
SPIDR	OTO1OII0	moderate	Biomarker	[24]
SUMO2	OT1Y5IKN	moderate	Genetic Variation	[25]
SUMO3	OTTUJQJ1	moderate	Genetic Variation	[25]
TCHP	OTVDMHSY	moderate	Biomarker	[26]
TNMD	OTHLVA9G	moderate	Biomarker	[27]
TOP3A	OT3CKUI9	moderate	Genetic Variation	[28]
APOBEC3C	OTPL0AI1	Strong	Genetic Variation	[29]
ARID5A	OTQT7CG9	Strong	Biomarker	[30]
CYCS	OTBFALJD	Strong	Biomarker	[31]
DNA2	OT4DJFFU	Strong	Genetic Variation	[32]
EXO1	OTI87RS5	Strong	Biomarker	[32]
FANCC	OTTIDM3P	Strong	Genetic Variation	[33]
FANCM	OTNJG99Z	Strong	Biomarker	[34]
GYPA	OTABU4YV	Strong	Biomarker	[35]
HFM1	OTHV3EFE	Strong	Biomarker	[36]
IFT80	OTMH0MBI	Strong	Genetic Variation	[37]
LBR	OT1HG3HG	Strong	Biomarker	[38]
LTBP4	OTC8WL2V	Strong	Altered Expression	[39]
MUS81	OTVZ4E60	Strong	Biomarker	[23]
RECQL4	OT59LSW7	Strong	Biomarker	[8]
SMR3A	OT6NAJJI	Strong	Genetic Variation	[29]
TOPBP1	OT6UPZPD	Strong	Biomarker	[40]
BLM	OTEJOAJX	Definitive	Autosomal recessive	[41]
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⏷ Show the Full List of 40 DOT(s)

References

1	Fanconi anemia and Bloom's syndrome crosstalk through FANCJ-BLM helicase interaction.Trends Genet. 2012 Jan;28(1):7-13. doi: 10.1016/j.tig.2011.09.003. Epub 2011 Oct 23.
2	Cytidine Deaminase Deficiency Reveals New Therapeutic Opportunities against Cancer.Clin Cancer Res. 2017 Apr 15;23(8):2116-2126. doi: 10.1158/1078-0432.CCR-16-0626. Epub 2016 Sep 6.
3	FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia.Mol Cell. 2009 Dec 25;36(6):943-53. doi: 10.1016/j.molcel.2009.12.006.
4	Relationship between platelet activation related factors and polymorphism of related genes in patients with coronary heart disease of blood-stasis syndrome.Chin J Integr Med. 2008 Dec;14(4):267-73. doi: 10.1007/s11655-008-0267-1. Epub 2008 Dec 12.
5	Cangrelor alleviates pulmonary fibrosis by inhibiting GPR17-mediated inflammation in mice.Int Immunopharmacol. 2018 Sep;62:261-269. doi: 10.1016/j.intimp.2018.06.006. Epub 2018 Jul 23.
6	TopBP1 interacts with BLM to maintain genome stability but is dispensable for preventing BLM degradation.Mol Cell. 2015 Mar 19;57(6):1133-1141. doi: 10.1016/j.molcel.2015.02.012.
7	Molecular genetics of Bloom's syndrome.Hum Mol Genet. 1996;5 Spec No:1457-63. doi: 10.1093/hmg/5.supplement_1.1457.
8	Bloom's syndrome: Why not premature aging?: A comparison of the BLM and WRN helicases.Ageing Res Rev. 2017 Jan;33:36-51. doi: 10.1016/j.arr.2016.05.010. Epub 2016 May 26.
9	Melanoma cell-derived vascular endothelial growth factor induces endothelial tubulogenesis within fibrin gels by a metalloproteinase-mediated mechanism.Eur J Cell Biol. 2006 Nov;85(11):1167-77. doi: 10.1016/j.ejcb.2006.07.003. Epub 2006 Sep 1.
10	Biological activities of phosphocitrate: a potential meniscal protective agent.Biomed Res Int. 2013;2013:726581. doi: 10.1155/2013/726581. Epub 2013 Jul 11.
11	Role for RIF1-interacting partner DDX1 in BLM recruitment to DNA double-strand breaks.DNA Repair (Amst). 2017 Jul;55:47-63. doi: 10.1016/j.dnarep.2017.05.001. Epub 2017 May 13.
12	Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom's syndrome, suggest a role in recombination during meiotic prophase.J Cell Sci. 2000 Feb;113 ( Pt 4):663-72. doi: 10.1242/jcs.113.4.663.
13	Chromosomal aberrations in Bloom syndrome patients with myeloid malignancies.Cancer Genet Cytogenet. 2001 Jul 1;128(1):39-42. doi: 10.1016/s0165-4608(01)00392-2.
14	Evidence for increased in vivo mutation and somatic recombination in Bloom's syndrome.Proc Natl Acad Sci U S A. 1989 Jan;86(2):670-4. doi: 10.1073/pnas.86.2.670.
15	Molecular advances in genetic skin diseases.Curr Opin Pediatr. 2002 Aug;14(4):419-25. doi: 10.1097/00008480-200208000-00011.
16	Decreased expression of MS4A12 inhibits differentiation and predicts early stage survival in colon cancer.Neoplasma. 2017;64(1):65-73. doi: 10.4149/neo_2017_108.
17	P311 Promotes Lung Fibrosis via Stimulation of Transforming Growth Factor-1, -2, and -3 Translation.Am J Respir Cell Mol Biol. 2019 Feb;60(2):221-231. doi: 10.1165/rcmb.2018-0028OC.
18	Lung inflammation after bleomycin treatment in mice: Selection of an accurate normalization strategy for gene expression analysis in an ex-vivo and in-vitro model.Int J Biochem Cell Biol. 2017 Jul;88:145-154. doi: 10.1016/j.biocel.2017.05.016. Epub 2017 May 16.
19	The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase delta.Nucleic Acids Res. 2008 Sep;36(16):5166-79. doi: 10.1093/nar/gkn498. Epub 2008 Aug 5.
20	Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D).J Biol Chem. 2003 Nov 28;278(48):48357-66. doi: 10.1074/jbc.M308838200. Epub 2003 Sep 15.
21	hRAD54 gene and 1p high-resolution deletion-mapping analyses in oligodendrogliomas.Cancer Genet Cytogenet. 2000 Jan 15;116(2):142-7. doi: 10.1016/s0165-4608(99)00122-3.
22	Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.PLoS Genet. 2016 Dec 15;12(12):e1006483. doi: 10.1371/journal.pgen.1006483. eCollection 2016 Dec.
23	Aberrant chromosome morphology in human cells defective for Holliday junction resolution.Nature. 2011 Mar 31;471(7340):642-6. doi: 10.1038/nature09790. Epub 2011 Mar 13.
24	Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10646-51. doi: 10.1073/pnas.1220921110. Epub 2013 Mar 18.
25	Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification.J Biol Chem. 2008 Oct 24;283(43):29405-15. doi: 10.1074/jbc.M803632200. Epub 2008 Aug 15.
26	Absence of p53 enhances growth defects and etoposide sensitivity of human cells lacking the Bloom syndrome helicase BLM.DNA Cell Biol. 2007 Jul;26(7):517-25. doi: 10.1089/dna.2007.0578.
27	The role of the secondary phloem during the development of the grapevine Berry Shrivel ripening disorder.Micron. 2019 Jan;116:36-45. doi: 10.1016/j.micron.2018.09.012. Epub 2018 Sep 27.
28	Mutations in TOP3A Cause a Bloom Syndrome-like Disorder.Am J Hum Genet. 2018 Aug 2;103(2):221-231. doi: 10.1016/j.ajhg.2018.07.001. Epub 2018 Jul 26.
29	Percutaneous interventional management of biliary complications after pediatric liver transplantation: A 16-year single-institution experience.Pediatr Transplant. 2017 Feb;21(1). doi: 10.1111/petr.12837. Epub 2016 Oct 30.
30	Arid5a-deficient mice are highly resistant to bleomycin-induced lung injury.Int Immunol. 2017 Feb 1;29(2):79-85. doi: 10.1093/intimm/dxx004.
31	Long term follow-up of Behet's syndrome patients treated with cyclophosphamide.Rheumatology (Oxford). 2020 Sep 1;59(9):2264-2271. doi: 10.1093/rheumatology/kez598.
32	RPA Phosphorylation Inhibits DNA Resection.Mol Cell. 2019 Jul 11;75(1):145-153.e5. doi: 10.1016/j.molcel.2019.05.005. Epub 2019 May 29.
33	Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles.PLoS Genet. 2012 Sep;8(9):e1002894. doi: 10.1371/journal.pgen.1002894. Epub 2012 Sep 27.
34	Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome.Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4437-42. doi: 10.1073/pnas.1117279109. Epub 2012 Mar 5.
35	In vivo somatic mutations in Werner's syndrome.Hum Genet. 1998 Oct;103(4):405-10. doi: 10.1007/s004390050841.
36	The Werner syndrome RECQ helicase targets G4 DNA in human cells to modulate transcription.Hum Mol Genet. 2016 May 15;25(10):2060-2069. doi: 10.1093/hmg/ddw079. Epub 2016 Mar 16.
37	Mutations in IFT80 cause SRPS Type IV. Report of two families and review. Am J Med Genet A. 2019 Apr;179(4):639-644. doi: 10.1002/ajmg.a.61050. Epub 2019 Feb 14.
38	Dominant negative effect of novel mutations in pyruvate kinase-M2.DNA Cell Biol. 2004 Jul;23(7):442-9. doi: 10.1089/1044549041474797.
39	Increased expression of latent TGF--binding protein 4 affects the fibrotic process in scleroderma by TGF-/SMAD signaling.Lab Invest. 2017 May;97(5):591-601. doi: 10.1038/labinvest.2017.20. Epub 2017 Mar 6.
40	Structural Insight into BLM Recognition by TopBP1.Structure. 2017 Oct 3;25(10):1582-1588.e3. doi: 10.1016/j.str.2017.08.005. Epub 2017 Sep 14.
41	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.