Details of Disease

Disease Name

Nijmegen breakage syndrome

immunodeficiency, microcephaly, and chromosomal instability; ataxia-telangiectasia variant V1; microcephaly with normal intelligence immunodeficiency and lymphoreticular malignancies; ataxia-telangiectasia variant V2; Nonsyndromal microcephaly autosomal recessive with normal intelligence; microcephaly immunodeficiency lymphoreticuloma; Seemanova syndrome 2; Nonsyndromal microcephaly, autosomal recessive, with normal intelligence; microcephaly with normal intelligence, immunodeficiency, and lymphoreticular malignancies; Nijmegen breakage syndrome; AT V1; NBs; Berlin breakage syndrome; Seemanova syndrome; Seemanova syndrome type 2; ataxia-telangiectasia, variant 1; microcephaly-immunodeficiency-lymphoreticuloma syndrome; immunodeficiency-microcephaly-chromosomal instability syndrome; microcephaly, normal intelligence and immunodeficiency

Definition

Nijmegen breakage syndrome is a rare genetic disease presenting at birth with microcephaly, dysmorphic facial features, becoming more noticeable with age, growth delay, and later-onset complications such as malignancies and infections.

Disease Hierarchy

DISCPWH9: Autosomal recessive disease

DISMFQKM: Developmental anomaly of metabolic origin

DISD0WVL: Multiple congenital anomalies/dysmorphic syndrome without intellectual disability

DISN7YWO: DNA repair disease

DIS98HVL: Nijmegen breakage syndrome

Disease Identifiers

MONDO ID

MONDO_0009623

MESH ID

D049932

UMLS CUI

C0398791

OMIM ID

251260

MedGen ID

140771

Orphanet ID

647

SNOMED CT ID

234638009

General Information of Disease (ID: DIS98HVL)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRIP1	TTZV7LJ	Strong	Genetic Variation	[1]
FANCF	TTNZKFJ	Strong	Biomarker	[2]
HCAR1	TTVK4ZO	Strong	Altered Expression	[3]
NME1	TTDY8JH	Strong	Altered Expression	[4]
TMPRSS2	TT1GM2Z	Strong	Genetic Variation	[5]
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This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MRE11	OTGU8TZM	Limited	Genetic Variation	[6]
RAD50	OTYMU9G1	Limited	Biomarker	[7]
ARID5B	OTUQ4CQY	Strong	Genetic Variation	[8]
ARL6	OTLV3SBS	Strong	Genetic Variation	[9]
BBS1	OTXSXB1K	Strong	Biomarker	[10]
BBS10	OTL1TTWX	Strong	Biomarker	[11]
BBS12	OT43DTAV	Strong	Genetic Variation	[12]
BBS2	OTPF9JIB	Strong	Genetic Variation	[9]
BBS4	OT0D3JC0	Strong	Genetic Variation	[9]
BBS7	OTELYWDQ	Strong	Genetic Variation	[13]
CBX5	OT8VYY84	Strong	Biomarker	[14]
IFT172	OT12DW08	Strong	Genetic Variation	[15]
KPNA2	OTU7FOE6	Strong	Altered Expression	[5]
LIG4	OT40DNXU	Strong	Genetic Variation	[16]
MKKS	OTLF5T11	Strong	Genetic Variation	[12]
MRPL36	OTZ9QV3U	Strong	Genetic Variation	[1]
NHEJ1	OTYOO05J	Strong	Genetic Variation	[17]
POLH	OTN07WXU	Strong	Genetic Variation	[18]
POLQ	OTBHK0E6	Strong	Genetic Variation	[18]
RAD52	OT0OTDHI	Strong	Biomarker	[19]
RAD54B	OTMWB2P2	Strong	Biomarker	[19]
SMC1A	OT9ZMRK9	Strong	Biomarker	[20]
TTC8	OTBGDZBD	Strong	Biomarker	[21]
NBN	OT73B5MD	Definitive	Autosomal recessive	[22]
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⏷ Show the Full List of 24 DOT(s)

References

1	Association of Single-Nucleotide Polymorphisms in Monoubiquitinated FANCD2-DNA Damage Repair Pathway Genes With Breast Cancer in the Chinese Population.Technol Cancer Res Treat. 2018 Jan 1;17:1533033818819841. doi: 10.1177/1533033818819841.
2	No evidence of significant silencing of Fanconi genes FANCF and FANCB or Nijmegen breakage syndrome gene NBS1 by DNA hyper-methylation in sporadic childhood leukaemia.Br J Haematol. 2006 Jul;134(1):61-3. doi: 10.1111/j.1365-2141.2006.06107.x.
3	Stimulation of lactate receptor (HCAR1) affects cellular DNA repair capacity.DNA Repair (Amst). 2017 Apr;52:49-58. doi: 10.1016/j.dnarep.2017.02.007. Epub 2017 Feb 20.
4	The Effect of an Orthotic Device for Balancing Neck Muscles During Daily Office Tasks.Hum Factors. 2019 Aug;61(5):722-735. doi: 10.1177/0018720818814957. Epub 2019 Jan 4.
5	The prognostic impact of high Nijmegen breakage syndrome (NBS1) gene expression in ERG-negative prostate cancers lacking PTEN deletion is driven by KPNA2 expression.Int J Cancer. 2014 Sep 15;135(6):1399-407. doi: 10.1002/ijc.28778. Epub 2014 Feb 26.
6	Contribution of Double-strand Break Repair Gene Nijmegen Breakage Syndrome 1 Genotypes, Gender Difference and Smoking Status to Taiwanese Lung Cancer.Anticancer Res. 2017 May;37(5):2417-2423. doi: 10.21873/anticanres.11581.
7	Poly(ADP-ribose) polymerase-1 promotes recruitment of meiotic recombination-11 to chromatin and DNA double-strand break repair in Ku70-deficient breast cancer cells.FASEB J. 2018 Jun 6:fj201800092R. doi: 10.1096/fj.201800092R. Online ahead of print.
8	Role of 657del5 NBN mutation and 7p12.2 (IKZF1), 9p21 (CDKN2A), 10q21.2 (ARID5B) and 14q11.2 (CEBPE) variation and risk of childhood ALL in the Polish population.Leuk Res. 2011 Nov;35(11):1534-6. doi: 10.1016/j.leukres.2011.07.034. Epub 2011 Sep 1.
9	Genetic heterogeneity of Bardet-Biedl syndrome in a distinct Canadian population: evidence for a fifth locus.Genomics. 1999 Jan 1;55(1):2-9. doi: 10.1006/geno.1998.5626.
10	Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome.Am J Hum Genet. 2003 May;72(5):1187-99. doi: 10.1086/375178. Epub 2003 Apr 3.
11	BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet. 2006 May;38(5):521-4. doi: 10.1038/ng1771. Epub 2006 Apr 2.
12	Bardet-Biedl Syndrome as a Chaperonopathy: Dissecting the Major Role of Chaperonin-Like BBS Proteins (BBS6-BBS10-BBS12).Front Mol Biosci. 2017 Jul 31;4:55. doi: 10.3389/fmolb.2017.00055. eCollection 2017.
13	Bardet-Biedl Syndrome in rhesus macaques: A nonhuman primate model of retinitis pigmentosa.Exp Eye Res. 2019 Dec;189:107825. doi: 10.1016/j.exer.2019.107825. Epub 2019 Oct 4.
14	NBS1 interacts with HP1 to ensure genome integrity.Cell Death Dis. 2019 Dec 13;10(12):951. doi: 10.1038/s41419-019-2185-x.
15	Identification of a novel mutation confirms the implication of IFT172 (BBS20) in Bardet-Biedl syndrome.J Hum Genet. 2016 May;61(5):447-50. doi: 10.1038/jhg.2015.162. Epub 2016 Jan 14.
16	Rubella Virus-Associated Cutaneous Granulomatous Disease: a Unique Complication in Immune-Deficient Patients, Not Limited to DNA Repair Disorders.J Clin Immunol. 2019 Jan;39(1):81-89. doi: 10.1007/s10875-018-0581-0. Epub 2019 Jan 3.
17	Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype.Hum Mutat. 2010 Sep;31(9):1059-68. doi: 10.1002/humu.21315.
18	Parkin regulates translesion DNA synthesis in response to UV radiation.Oncotarget. 2017 May 30;8(22):36423-36437. doi: 10.18632/oncotarget.16855.
19	Nijmegen breakage syndrome gene (NBS1) is not the tumor suppressor gene at 8q21.3 involved in colorectal carcinoma.Oncol Rep. 2002 Jul-Aug;9(4):709-11.
20	The Major Tegument Protein of Bovine Herpesvirus 1, VP8, Interacts with DNA Damage Response Proteins and Induces Apoptosis.J Virol. 2018 Jul 17;92(15):e00773-18. doi: 10.1128/JVI.00773-18. Print 2018 Aug 1.
21	BBS7 and TTC8 (BBS8) mutations play a minor role in the mutational load of Bardet-Biedl syndrome in a multiethnic population.Hum Mutat. 2009 Jul;30(7):E737-46. doi: 10.1002/humu.21040.
22	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.