644 results match your criteria Nijmegen Breakage Syndrome


Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome.

J Clin Immunol 2020 Jun 30. Epub 2020 Jun 30.

Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Samory Mashela str, Moscow, Russia, 117997.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCRαβ/CD19+ graft depletion with fludarabine 150 mg/m, cyclophosphamide 20-40 mg/kg and thymoglobulin 5 mg/kg based conditioning regimens (CRs). Read More

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http://dx.doi.org/10.1007/s10875-020-00811-9DOI Listing

Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome.

Aging (Albany NY) 2020 Jun 20;12(12):12342-12375. Epub 2020 Jun 20.

Institute of Clinical Chemistry and Laboratory Medicine, University of Rostock, Rostock, Germany.

Background: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy.

Results: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by ~40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (~25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL. Read More

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http://dx.doi.org/10.18632/aging.103453DOI Listing

Nijmegen breakage syndrome: case report and review of literature.

Pan Afr Med J 2020 20;35:85. Epub 2020 Mar 20.

Department of Pediatrics, Military Teaching Hospital Mohammed V, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.

Nijmegen Breakage Syndrome (NBS) is a rare autosomalrecessive DNA repair disorder characterized by genomic instability andincreased risk of haematopoietic malignancies observed in morethan 40% of the patients by the time they are 20 years old. The underlying gene, NBS1, is located on human chromosome 8q21 and codes for a protein product termed nibrin, Nbs1 or p95. Over 90% of patients are homozygous for a founder mutation: a deletion of five base pairs which leads to a frame shift and protein truncation. Read More

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http://dx.doi.org/10.11604/pamj.2020.35.85.14746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250236PMC

Evaluation of awareness about primary immunodeficiencies among physicians before and after implementation of the educational program: A longitudinal study.

PLoS One 2020 29;15(5):e0233342. Epub 2020 May 29.

Department of Children's Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.

Increasing physicians' awareness is one of the main ways to improve early diagnosis of rare diseases. A survey among physicians of different specialties to evaluate the knowledge about primary immunodeficiencies (PID) was conducted in 2016 and in 2019 -before and after the implementation of an educational program. We compare responses from 82 doctors who participated in the 2016 survey, and 67 doctors who have taken part in the survey in 2019: pediatricians, general practitioners / family physicians and physicians of pediatric sub specialties. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233342PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259605PMC

Association of Nijmegen Breakage Syndrome 1 Genotypes With Bladder Cancer Risk.

Anticancer Res 2020 Apr;40(4):2011-2017

Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Background/aim: We aimed to examine the association of the genotypes of Nijmegen breakage syndrome 1 (NBS1), a critical gene in DNA double strand break repair machinery, with bladder cancer risk in Taiwan.

Materials And Methods: NBS1 rs1805794 genotypes among 375 bladder cancer patients and 375 non-cancer healthy controls were determined via the polymerase chain reaction-restriction fragment length polymorphism methodology and their association with bladder cancer risk were evaluated.

Results: The results showed that the percentages of GG, CG and CC of NBS1 rs1805794 genotypes were 45. Read More

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http://dx.doi.org/10.21873/anticanres.14157DOI Listing
April 2020
1.872 Impact Factor

Human RAD50 deficiency: Confirmation of a distinctive phenotype.

Am J Med Genet A 2020 06 25;182(6):1378-1386. Epub 2020 Mar 25.

Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

DNA double-strand breaks (DSBs) are highly toxic DNA lesions that can lead to chromosomal instability, loss of genes and cancer. The MRE11/RAD50/NBN (MRN) complex is keystone involved in signaling processes inducing the repair of DSB by, for example, in activating pathways leading to homologous recombination repair and nonhomologous end joining. Additionally, the MRN complex also plays an important role in the maintenance of telomeres and can act as a stabilizer at replication forks. Read More

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http://dx.doi.org/10.1002/ajmg.a.61570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318339PMC

Modeling cancer genomic data in yeast reveals selection against ATM function during tumorigenesis.

PLoS Genet 2020 03 18;16(3):e1008422. Epub 2020 Mar 18.

Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

The DNA damage response (DDR) comprises multiple functions that collectively preserve genomic integrity and suppress tumorigenesis. The Mre11 complex and ATM govern a major axis of the DDR and several lines of evidence implicate that axis in tumor suppression. Components of the Mre11 complex are mutated in approximately five percent of human cancers. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105138PMC

Chromothripsis and DNA Repair Disorders.

J Clin Med 2020 Feb 25;9(3). Epub 2020 Feb 25.

Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements, resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells, resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Read More

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http://dx.doi.org/10.3390/jcm9030613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141117PMC
February 2020

Hematopoietic Stem Cell Transplantation for DNA Double Strand Breakage Repair Disorders.

Front Pediatr 2019 15;7:557. Epub 2020 Jan 15.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

The ubiquitous presence of enzymes required for repair of DNA double strand breaks renders patients with defects in these pathways susceptible to immunodeficiency, an increased risk of infection, autoimmunity, bone marrow failure and malignancies, which are commonly associated with Epstein Barr virus (EBV) infection. Treatment of malignancies is particularly difficult, as the nature of the systemic defect means that patients are sensitive to chemotherapy and radiotherapy. Increasing numbers of patients with Nijmegen Breakage syndrome, Ligase 4 deficiency and Cernunnos-XLF deficiency have been successfully transplanted. Read More

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http://dx.doi.org/10.3389/fped.2019.00557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974535PMC
January 2020

Complex profile of multiple hepatobiliary and gastrointestinal complications after hematopoietic stem cell transplantation in a child with Nijmegen breakage syndrome.

Cent Eur J Immunol 2019 30;44(3):327-331. Epub 2019 Sep 30.

Department of Paediatrics, Haematology and Oncology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Antoni Jurasz University Hospital No. 1, Bydgoszcz, Poland.

Patients with Nijmegen breakage syndrome (NBS) can develop life-threatening immunodeficiency, which should be treated with hematopoietic stem cell transplantation (HSCT). We report the case of a 14-year-old girl with NBS who due to an increasing number of severe complications was referred for HSCT from a matched unrelated donor. After reduced-intensity conditioning and transplantation of peripheral blood hematopoietic cells, during the early post-transplant period (days 0-30), the girl suffered from severe mucositis, fever episodes, mild acute renal injury and facial vasculitis. Read More

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http://dx.doi.org/10.5114/ceji.2019.89612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925563PMC
September 2019

NBS1 interacts with HP1 to ensure genome integrity.

Cell Death Dis 2019 12 13;10(12):951. Epub 2019 Dec 13.

Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Rome, Italy.

Heterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD). Read More

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http://dx.doi.org/10.1038/s41419-019-2185-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911104PMC
December 2019

Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders.

Front Genet 2019 7;10:1092. Epub 2019 Nov 7.

AGE Research Group, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.

Evidence from multiple laboratories has accumulated to show that mosaic neuronal aneuploidy and consequent apoptosis characterizes and may underlie neuronal loss in many neurodegenerative diseases, particularly Alzheimer's disease and frontotemporal dementia. Furthermore, several neurodevelopmental disorders, including Seckel syndrome, ataxia telangiectasia, Nijmegen breakage syndrome, Niemann-Pick type C, and Down syndrome, have been shown to also exhibit mosaic aneuploidy in neurons in the brain and in other cells throughout the body. Together, these results indicate that both neurodegenerative and neurodevelopmental disorders with apparently different pathogenic causes share a cell cycle defect that leads to mosaic aneuploidy in many cell types. Read More

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http://dx.doi.org/10.3389/fgene.2019.01092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855267PMC
November 2019

DNA repair functional analyses of NBN hypomorphic variants associated with NBN-related infertility.

Hum Mutat 2020 Mar 28;41(3):608-618. Epub 2019 Nov 28.

INSERM U830, Institut Curie, PSL Research University, Paris, France.

Nijmegen breakage syndrome caused by biallelic pathogenic variants of the DNA-damage response gene NBN, is characterized by severe microcephaly, cancer proneness, infertility, and karyotype abnormalities. We previously reported NBN variants in siblings suffering from fertility defects. Here, we identify a new founder NBN variant (c. Read More

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http://dx.doi.org/10.1002/humu.23955DOI Listing

E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair.

Nat Commun 2019 10 30;10(1):4951. Epub 2019 Oct 30.

Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX, 78957, USA.

E2F1 and retinoblastoma (RB) tumor-suppressor protein not only regulate the periodic expression of genes important for cell proliferation, but also localize to DNA double-strand breaks (DSBs) to promote repair. E2F1 is acetylated in response to DNA damage but the role this plays in DNA repair is unknown. Here we demonstrate that E2F1 acetylation creates a binding motif for the bromodomains of the p300/KAT3B and CBP/KAT3A acetyltransferases and that this interaction is required for the recruitment of p300 and CBP to DSBs and the induction of histone acetylation at sites of damage. Read More

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http://dx.doi.org/10.1038/s41467-019-12861-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821830PMC
October 2019

Antioxidant Defense, Redox Homeostasis, and Oxidative Damage in Children With Ataxia Telangiectasia and Nijmegen Breakage Syndrome.

Front Immunol 2019 27;10:2322. Epub 2019 Sep 27.

Department of Pediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, Bialystok, Poland.

Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Read More

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http://dx.doi.org/10.3389/fimmu.2019.02322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776633PMC
September 2019
1 Read

Chromosome instability syndromes.

Nat Rev Dis Primers 2019 09 19;5(1):64. Epub 2019 Sep 19.

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Fanconi anaemia (FA), ataxia telangiectasia (A-T), Nijmegen breakage syndrome (NBS) and Bloom syndrome (BS) are clinically distinct, chromosome instability (or breakage) disorders. Each disorder has its own pattern of chromosomal damage, with cells from these patients being hypersensitive to particular genotoxic drugs, indicating that the underlying defect in each case is likely to be different. In addition, each syndrome shows a predisposition to cancer. Read More

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http://dx.doi.org/10.1038/s41572-019-0113-0DOI Listing
September 2019
3 Reads

Nbn-Mre11 interaction is required for tumor suppression and genomic integrity.

Proc Natl Acad Sci U S A 2019 07 8;116(30):15178-15183. Epub 2019 Jul 8.

Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;

We derived a mouse model in which a mutant form of Nbn/Nbs1 (hereafter Nbn) exhibits severely impaired binding to the Mre11-Rad50 core of the Mre11 complex. The allele was expressed exclusively in hematopoietic lineages (in mice). Unlike mice with Nbn deficiency in the bone marrow, mice were viable. Read More

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http://dx.doi.org/10.1073/pnas.1905305116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660787PMC
July 2019
2 Reads

A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management.

Gynecol Endocrinol 2019 Nov 12;35(11):999-1002. Epub 2019 Jun 12.

Department of Gynecological Endocrinology, Poznan University of Medical Sciences , Poznan , Poland.

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS. Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed. Read More

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http://dx.doi.org/10.1080/09513590.2019.1626366DOI Listing
November 2019
23 Reads

Two novel variants in the ATM gene causing ataxia-telangiectasia, including a duplication of 90 kb: Utility of targeted next-generation sequencing in detection of copy number variation.

Ann Hum Genet 2019 07 19;83(4):266-273. Epub 2019 Mar 19.

Department of Biomedical Diagnostics, Hospital San Pedro, Logroño, Spain.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, ocular apraxia, immunodeficiency, telangiectasia, elevated serum α-fetoprotein concentration, radiosensitivity and cancer predisposition. Classical A-T is caused by biallelic variants on ATM (ataxia telangiectasia mutated) gene, leading to a loss of function of the protein kinase ATM, involved in DNA damage repair. Atypical presentations can be found in A-T-like disease or in Nijmegen breakage syndrome, caused by deficiency of mre11 or nibrin proteins, respectively. Read More

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http://dx.doi.org/10.1111/ahg.12312DOI Listing
July 2019
18 Reads

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 01;17:1533033818819841

1 Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Objective: The aim of the study was to estimate breast cancer risk conferred by individual single-nucleotide polymorphisms of breast cancer susceptibility genes.

Methods: We analyzed the 48 tagging single-nucleotide polymorphisms of 8 breast cancer susceptibility genes involved in the monoubiquitinated FANCD2-DNA damage repair pathway in 734 Chinese women with breast cancer and 672 age-matched healthy controls.

Results: Forty-five tagging single-nucleotide polymorphisms were successfully genotyped by SNPscan, and the call rates for each tagging single-nucleotide polymorphisms were above 98. Read More

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http://dx.doi.org/10.1177/1533033818819841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311543PMC
January 2018
19 Reads

Fibroblast-derived integration-free iPSC line ISRM-NBS1 from an 18-year-old Nijmegen Breakage Syndrome patient carrying the homozygous NBN c.657_661del5 mutation.

Stem Cell Res 2019 01 27;34:101372. Epub 2018 Dec 27.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address:

Human fibroblasts cells from a female diagnosed with Nijmegen Breakage Syndrome (NBS) carrying the homozygous NBN c.657_661del5 mutation were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, NANOG, KLF4, c-MYC and LIN28. The derived iPSC line - ISRM-NBS1 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0. Read More

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http://dx.doi.org/10.1016/j.scr.2018.101372DOI Listing
January 2019
7 Reads

Rubella Virus-Associated Cutaneous Granulomatous Disease: a Unique Complication in Immune-Deficient Patients, Not Limited to DNA Repair Disorders.

J Clin Immunol 2019 01 3;39(1):81-89. Epub 2019 Jan 3.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Department of Pediatrics, University of Washington, Seattle, WA, USA.

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). Read More

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http://link.springer.com/10.1007/s10875-018-0581-0
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http://dx.doi.org/10.1007/s10875-018-0581-0DOI Listing
January 2019
48 Reads

Radiogenomics.

Med Phys 2018 Nov;45(11):e1111-e1122

Trento Institute for Fundamental Physics Applications, National Institute for Nuclear Physics, Trento, Italy.

Purpose: Radiogenomics is the study of genomic changes that underlie the radioresponse of normal and tumor tissues. And while this is generally regarded as a whole genome approach, one must keep in mind the impact of single gene biology on radioresponse, (ataxia telangiectasia, Nijmegen breakage syndrome).

Methods: This review begins with the association of single nucleotide polymorphisms in the DNA with adverse normal tissue events to the prediction of therapeutic outcome after radiotherapy. Read More

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http://doi.wiley.com/10.1002/mp.13064
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http://dx.doi.org/10.1002/mp.13064DOI Listing
November 2018
12 Reads

Nijmegen Breakage Syndrome Complicated With Primary Pulmonary Granulomas.

Pediatrics 2018 10 12;142(4). Epub 2018 Sep 12.

Departments of Pulmonology and Allergy and

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease characterized by microcephaly, growth retardation, severe immunodeficiency, and predisposition to lymphoid malignancy. In this report, we describe a case of a 9-year-old boy, previously diagnosed with NBS and symptoms of dyspnea, dry cough, and fever. Despite initial recognition of pneumonia, there was no response to broad spectrum antimicrobial treatment, negative results from microbiological tests, and unclear changes in lung imaging were observed. Read More

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http://dx.doi.org/10.1542/peds.2018-0122DOI Listing
October 2018
10 Reads

Case 1: Microcephaly, Skeletal Dysplasia, and Immunodeficiency in a Newborn.

Pediatr Rev 2018 Jul;39(7):359-362

Department of Medical Genetics and Genomic Medicine, Saint Peter's University Hospital, New Brunswick, NJ.

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http://dx.doi.org/10.1542/pir.2017-0101DOI Listing
July 2018
12 Reads

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. Epub 2018 Jun 6.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Poly(ADP-ribose) polymerase (PARP)-1 may act in an error-prone pathway called alternative end joining (Alt-EJ) for DNA double-strand break (DSB) repair when nonhomologous end joining is defective. We examined the recruitment of PARP-1 to chromatin in response to radiomimetic agents and the effects of PARP-1 inhibition on DSB repair and recruitment of the meiotic recombination (MRE)-11-double-strand break repair (RAD50) protein-Nijmegen breakage syndrome (NSB)-1 (MRN) complex to the chromatin in Ku70-deficient breast cancer cells. The chromatin-binding affinity of PARP-1 was enhanced in response to neocarzinostatin (NCS) or calicheamicin treatment in the absence of Ku70. Read More

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http://dx.doi.org/10.1096/fj.201800092RDOI Listing
June 2018
5 Reads

The Major Tegument Protein of Bovine Herpesvirus 1, VP8, Interacts with DNA Damage Response Proteins and Induces Apoptosis.

J Virol 2018 08 17;92(15). Epub 2018 Jul 17.

VIDO-InterVac, University of Saskatchewan, Saskatoon, SK, Canada

VP8, the gene product in bovine herpesvirus-1 (BoHV-1), is a major tegument protein that is essential for virus replication The major DNA damage response protein, ataxia telangiectasia mutated (ATM), phosphorylates Nijmegen breakage syndrome (NBS1) and structural maintenance of chromosome-1 (SMC1) proteins during the DNA damage response. VP8 was found to interact with ATM and NBS1 during transfection and BoHV-1 infection. However, VP8 did not interfere with phosphorylation of ATM in transfected or BoHV-1-infected cells. Read More

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http://dx.doi.org/10.1128/JVI.00773-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052309PMC
August 2018
17 Reads

Correction to: Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence.

J Clin Immunol 2018 May;38(4):538

Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015, CN, Rotterdam, The Netherlands.

The original version of the article, "Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence" incorrectly listed the affiliation of the fourth author, Iwona Solarska. The correct affiliation is "Molecular Biology Laboratory, Institute of Hematology and Transfusion Medicine. Read More

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http://dx.doi.org/10.1007/s10875-018-0503-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828370PMC
May 2018
14 Reads

The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.

Annu Rev Biochem 2018 06 25;87:263-294. Epub 2018 Apr 25.

Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA; email: ,

Genomic instability in disease and its fidelity in health depend on the DNA damage response (DDR), regulated in part from the complex of meiotic recombination 11 homolog 1 (MRE11), ATP-binding cassette-ATPase (RAD50), and phosphopeptide-binding Nijmegen breakage syndrome protein 1 (NBS1). The MRE11-RAD50-NBS1 (MRN) complex forms a multifunctional DDR machine. Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076887PMC
June 2018
6 Reads

Identification of variants in pleiotropic genes causing "isolated" premature ovarian insufficiency: implications for medical practice.

Eur J Hum Genet 2018 09 30;26(9):1319-1328. Epub 2018 Apr 30.

Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.

Next-generation sequencing (NGS) is increasingly being used in a clinical setting for the molecular diagnosis of patients with heterogeneous disorders, such as premature ovarian insufficiency (POI). We performed NGS of ~1000 candidate genes in four unrelated patients with POI. We discovered the genetic cause of "isolated" POI in two cases, both of which had causative variants in surprising genes. Read More

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http://dx.doi.org/10.1038/s41431-018-0140-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117257PMC
September 2018
4 Reads

Association of 17q24.2-q24.3 deletions with recognizable phenotype and short telomeres.

Am J Med Genet A 2018 06 25;176(6):1438-1442. Epub 2018 Apr 25.

Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.

Microdeletions of 17q24.2-q24.3 have been described in several patients with developmental and speech delay, growth retardation, and other features. Read More

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http://dx.doi.org/10.1002/ajmg.a.38711DOI Listing
June 2018
17 Reads

Interdependent and separable functions of MRN-C complex members couple formation and repair of meiotic DSBs.

Proc Natl Acad Sci U S A 2018 05 23;115(19):E4443-E4452. Epub 2018 Apr 23.

Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305;

Faithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which, in turn, relies on the formation and repair of numerous double-strand breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here, we identify NBS-1, the ortholog of the NBS1 (mutated in Nijmegen Breakage Syndrome) subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis. Read More

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http://dx.doi.org/10.1073/pnas.1719029115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948970PMC
May 2018
7 Reads

Genetic testing for hereditary prostate cancer: Current status and limitations.

Cancer 2018 08 18;124(15):3105-3117. Epub 2018 Apr 18.

Department of Urology, Yale School of Medicine, New Haven, Connecticut.

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. Read More

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http://dx.doi.org/10.1002/cncr.31316DOI Listing
August 2018
13 Reads
4.889 Impact Factor

Comparison of Selected Parameters of Redox Homeostasis in Patients with Ataxia-Telangiectasia and Nijmegen Breakage Syndrome.

Oxid Med Cell Longev 2017 31;2017:6745840. Epub 2017 Dec 31.

Department of Pediatrics Rheumatology, Immunology, and Metabolic Bone Diseases, Medical University of Bialystok, Waszyngtona 17 Str., 15-274 Bialystok, Poland.

This study compared the antioxidant status and major lipophilic antioxidants in patients with ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS). Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and concentrations of coenzyme Q10 (CoQ10) and vitamins A and E were estimated in the plasma of 22 patients with AT, 12 children with NBS, and the healthy controls. In AT patients, TAS (median 261. Read More

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http://dx.doi.org/10.1155/2017/6745840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804414PMC
October 2018
28 Reads

Evidence for a pre-malignant cell line in a skin biopsy from a patient with Nijmegen breakage syndrome.

Mol Cytogenet 2018 7;11:17. Epub 2018 Feb 7.

4Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.

Background: Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to X-irradiation, and a high predisposition to cancer. Nibrin, the product of the gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of DNA double strand breaks (DSBs), and plays a critical role in the processing of DSBs in immune gene rearrangements, telomere maintenance, and meiotic recombination. NBS skin fibroblasts grow slowly in culture and enter early into senescence. Read More

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https://molecularcytogenetics.biomedcentral.com/articles/10.
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http://dx.doi.org/10.1186/s13039-018-0364-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803995PMC
February 2018
105 Reads

NBS1 rs2735383 polymorphism is associated with an increased risk of laryngeal carcinoma.

BMC Cancer 2018 02 12;18(1):175. Epub 2018 Feb 12.

School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.

Background: Nijmegen breakage syndrome 1 (NBS1), as a key protein in the DNA double-strand breaks (DSBs) repair pathway, plays an important role in maintaining genomic stability. Although single nucleotide polymorphisms (SNPs) in NBS1 have frequently been studied in multiple cancers, the relationships of two functional NBS1 polymorphisms (rs2735383 and rs1805794) with laryngeal carcinoma are yet unclear. Therefore, in the present study, we performed a case-control study including 342 cases and 345 controls to analyze the associations between two polymorphisms of NBS1 and the risk of laryngeal carcinoma. Read More

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http://dx.doi.org/10.1186/s12885-018-4078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810033PMC
February 2018
7 Reads

A non-synonymous polymorphism in is associated with progression from chronic hepatitis B virus infection to hepatocellular carcinoma in a Chinese population.

Onco Targets Ther 2018 26;11:563-569. Epub 2018 Jan 26.

Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan.

Purpose: Nijmegen breakage syndrome 1 (NBS1) has a vital role in DNA double-strand break (DSB) repair, functioning as a sensor to identify and repair DNA damage and maintaining genomic stability by participating in the intra-S-phase checkpoint. Polymorphisms of NBS1 have been investigated in multiple cancers with variable results. To our best knowledge, no previous study has focused on the association between single-nucleotide polymorphisms (SNPs) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Read More

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http://dx.doi.org/10.2147/OTT.S153538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790086PMC
January 2018
11 Reads

Inactivation of ribosomal protein S27-like confers radiosensitivity via the Mdm2-p53 and Mdm2-MRN-ATM axes.

Cell Death Dis 2018 02 2;9(2):145. Epub 2018 Feb 2.

Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.

RPS27L (ribosomal protein S27-like) is an evolutionarily conserved ribosomal protein and a direct p53 target. We recently reported that Rps27l disruption triggers ribosomal stress to induce p53, causing postnatal death, which can be rescued by Trp53 . Whether and how Rps27l modulates radiosensitivity is unknown. Read More

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http://dx.doi.org/10.1038/s41419-017-0192-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833388PMC
February 2018
2 Reads

Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks.

Nat Cell Biol 2017 Dec 27;19(12):1400-1411. Epub 2017 Nov 27.

IFOM-The FIRC Institute of Molecular Oncology, Milan 20139, Italy.

The DNA damage response (DDR) preserves genomic integrity. Small non-coding RNAs termed DDRNAs are generated at DNA double-strand breaks (DSBs) and are critical for DDR activation. Here we show that active DDRNAs specifically localize to their damaged homologous genomic sites in a transcription-dependent manner. Read More

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http://dx.doi.org/10.1038/ncb3643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714282PMC
December 2017
26 Reads

Reversible Hypogammaglobulinemia in 2 Pediatric Patients With Primary Immunodeficiency.

Authors:
S Pasic

J Investig Allergol Clin Immunol 2017;27(5):320-321

Department of Pediatric Immunology, Mother and Child Health Institute, School of Medicine, University of Belgrade, Serbia.

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http://www.jiaci.org/summary/vol27-issue5-num1532
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http://dx.doi.org/10.18176/jiaci.0173DOI Listing
July 2019
3 Reads

CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair.

Proc Natl Acad Sci U S A 2017 10 25;114(41):10912-10917. Epub 2017 Sep 25.

Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;

CTCF is an essential epigenetic regulator mediating chromatin insulation, long-range regulatory interactions, and the organization of large topological domains in the nucleus. Phenotypes of CTCF haploinsufficient mutations in humans, knockout in mice, and depletion in cells are often consistent with impaired genome stability, but a role of CTCF in genome maintenance has not been fully investigated. Here, we report that CTCF maintains genome stability, is recruited to sites of DNA damage, and promotes homologous recombination repair of DNA double-strand breaks (DSBs). Read More

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http://dx.doi.org/10.1073/pnas.1704076114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642685PMC
October 2017
19 Reads

Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae.

Am J Med Genet A 2017 Nov 28;173(11):3075-3081. Epub 2017 Sep 28.

Division of Genetics, Department of Pediatrics, University of California, San Francisco, California.

We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11. After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants-c.1523T>G, predicting (p. Read More

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http://dx.doi.org/10.1002/ajmg.a.38382DOI Listing
November 2017
23 Reads

MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress.

Cancer Res 2017 10 17;77(19):5327-5338. Epub 2017 Aug 17.

Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan.

Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes. MRN binds DNA double-strand breaks, where it functions in repair and triggers cell-cycle checkpoints via activation of the ataxia-telangiectasia mutated kinase. To gain understanding of MRN in cancer, we engineered mice with B lymphocytes lacking MRN, or harboring MRN in which MRE11 lacks nuclease activities. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-17-1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831255PMC
October 2017
27 Reads

Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT).

Front Immunol 2017 24;8:807. Epub 2017 Jul 24.

Dmitry Rogachev National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Background: Nijmegen breakage syndrome (NBS) is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Read More

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http://journal.frontiersin.org/article/10.3389/fimmu.2017.00
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http://dx.doi.org/10.3389/fimmu.2017.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523727PMC
July 2017
29 Reads

Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.

Sci Rep 2017 08 8;7(1):7516. Epub 2017 Aug 8.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, 40225, Düsseldorf, Germany.

Nijmegen Breakage Syndrome (NBS) is associated with cancer predisposition, premature aging, immune deficiency, microcephaly and is caused by mutations in the gene coding for NIBRIN (NBN) which is involved in DNA damage repair. Dermal-derived fibroblasts from NBS patients were reprogrammed into induced pluripotent stem cells (iPSCs) in order to bypass premature senescence. The influence of antioxidants on intracellular levels of ROS and DNA damage were screened and it was found that EDHB-an activator of the hypoxia pathway, decreased DNA damage in the presence of high oxidative stress. Read More

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http://dx.doi.org/10.1038/s41598-017-07905-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548734PMC
August 2017
12 Reads

Effects of Pulsed Electromagnetic Fields on Breast Cancer Cell Line MCF 7 Using Absorption Spectroscopy.

Anticancer Res 2017 07;37(7):3453-3459

Faculty of Science, Liverpool Hope University, Liverpool, U.K.

We present an analysis of the effects of pulsed electromagnetic fields (PEMF) with 3.3 MHz carrier frequency and modulated by audio resonant frequencies on the MCF-7 breast cancer cell line in vitro using absorption spectroscopy. This involves a fluorescence dye called PrestoBlue™ Cell Viability Reagent and a spectrophotometry to test the viability of MCF-7 breast cancer cells under different PEMF treatment conditions in terms of the cell absorption values. Read More

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http://ar.iiarjournals.org/content/37/7/3453.abstract
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http://dx.doi.org/10.21873/anticanres.11713DOI Listing
July 2017
13 Reads

Cancer predisposition syndromes associated with myeloid malignancy.

Semin Hematol 2017 04 7;54(2):115-122. Epub 2017 Apr 7.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN. Electronic address:

The majority of myeloid malignancies are caused by sporadic somatic events rather than cancer predisposition. Nonetheless, the identification of hereditary cancer predisposition syndromes is critical when caring for patients with myeloid malignancies since detection may direct decisions related to cancer treatment and surveillance. A positive genetic test result also has important implications for other family members who can use this information to undergo their own testing to determine their cancer risk. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00371963173004
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http://dx.doi.org/10.1053/j.seminhematol.2017.04.003DOI Listing
April 2017
6 Reads

Hsp90α regulates ATM and NBN functions in sensing and repair of DNA double-strand breaks.

FEBS J 2017 08 9;284(15):2378-2395. Epub 2017 Jul 9.

Department of Sciences, Roma Tre University, Roma, Italy.

The molecular chaperone heat shock protein 90 (Hsp90α) regulates cell proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Read More

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http://dx.doi.org/10.1111/febs.14145DOI Listing
August 2017
30 Reads