722 results match your criteria: "Nijmegen Breakage Syndrome"
NBS1 dePARylation by NUDT16 is critical for DNA double-strand break repair.
Mol Cell Biochem
October 2024
Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
NBS1, a protein linked to the autosomal recessive disorder Nijmegen breakage syndrome, plays an essential role in the DNA damage response and DNA repair. Despite its importance, the mechanisms regulating NBS1 and the impact of this regulation on DNA repair processes remain obscure. In this study, we discovered a new post-translational modification of NBS1, ADP-ribosylation.
View Article and Find Full Text PDFResolution of granulomatous lesions in a Nijmegen breakage syndrome patient with severe immunodeficiency after hematopoietic stem cell transplantation.
Pediatr Allergy Immunol
September 2024
Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czechia.
Update on Recommendations for Cancer Screening and Surveillance in Children with Genomic Instability Disorders.
Clin Cancer Res
November 2024
Division of Solid Tumor and Clinical Genetics, Department of Medicine and Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
Article Synopsis
- Genomic instability disorders involve DNA or chromosomal issues that can lead to developmental problems, immunodeficiency, and a higher likelihood of childhood cancers, along with extreme sensitivity to cancer treatments.
- The American Association of Cancer Research held a workshop in July 2023, where experts discussed updated guidelines for managing and monitoring children at risk for cancer due to these disorders.
- The article emphasizes the need to identify children with genomic instability disorders for accurate diagnosis, genetic counseling, and informed decisions regarding cancer screening and treatment options.
Liver Transplantation for Nijmegen Breakage Syndrome With Hepatic Malignancy and Hepatopulmonary Syndrome After Bone Marrow Transplantation: A Case Report.
Pediatr Transplant
November 2024
Liver Transplantation Center, School of Medicine, Koç University, Istanbul, Turkey.
Article Synopsis
- - Nijmegen breakage syndrome (NBS) is a severe genetic disorder characterized by DNA repair issues, leading to higher risks of infections, cancers, and poor overall prognosis; there is currently no specific treatment apart from occasional stem cell transplants.
- - A 14-year-old girl with NBS underwent a successful liver transplantation from her brother after suffering from severe liver issues linked to her condition, including potential malignancy.
- - Post-surgery, the patient showed no immediate complications and had a smooth recovery, with pathology revealing cancerous cells in her liver; this case suggests that liver transplantation can be an effective treatment option for NBS patients facing liver cancer.
Genetic hallmarks and clinical implications of chromothripsis in childhood T-cell acute lymphoblastic leukemia.
Leukemia
November 2024
Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland.
Chromothripsis (cth) is a form of genomic instability leading to massive de novo structural chromosome rearrangements in a one-time catastrophic event. It can cause cancer-promoting alterations, such as loss of sequences for tumor-suppressor genes, formation of oncogenic fusions, and oncogene amplifications. We investigated the genetic background and clinical significance of cth in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients.
View Article and Find Full Text PDFNijmegen breakage syndrome: 25-year experience of diagnosis and treatment in Ukraine.
Front Immunol
July 2024
Department of the Research and Biotechnology, Scientific Medical Genetic Center LeoGENE, Lviv, Ukraine.
Article Synopsis
- Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder primarily affecting Slavic populations, particularly in Ukraine, and is marked by symptoms such as microcephaly, immunodeficiency, and impaired DNA repair.
- A study of 84 NBS patients from Ukraine revealed that about 65.5% were alive, with a median age of 11 years; the prevalence of NBS diagnoses has shown a recent increase, especially from central and southeastern regions of the country.
- Clinical findings indicated that most patients experienced delayed physical development and infections, with malignancies (especially lymphomas) being a significant cause of death; immunological analysis showed reduced CD4+, CD19+, and immunoglobulin levels in the
NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.
Nature
July 2024
Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Article Synopsis
- The Warburg effect in cancer cells leads to glucose being metabolized anaerobically, resulting in lactate buildup, which impacts chemotherapy response and DNA repair processes.
- Lactate-induced lactylation of NBS1 is crucial for its role in DNA repair through homologous recombination and is influenced by specific enzymes that add or remove lactate.
- High lactylation levels of NBS1 correlate with poor chemotherapy outcomes, and reducing lactate through specific inhibitors may enhance treatment effectiveness by improving DNA repair mechanisms.
MRE11 is essential for the long-term viability of undifferentiated spermatogonia.
Cell Prolif
September 2024
Key Laboratory of Reproductive Genetics (Ministry of Education), Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
In the meiotic prophase, programmed SPO11-linked DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR). The MRE11-RAD50-NBS1 (MRN) complex is essential for initiating DNA end resection, the first step of HR. However, residual DNA end resection still occurs in Nbs1 knockout (KO) spermatocytes for unknown reasons.
View Article and Find Full Text PDFA Rare Case of Early T-Precursor Lymphoblastic Lymphoma (ETP-LBL) in a Child With Nijmegen Breakage Syndrome.
Pediatr Dev Pathol
November 2024
Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Article Synopsis
- - This text discusses a rare case of early T-precursor lymphoblastic lymphoma (ETP-LBL) in a patient with Nijmegen breakage syndrome (NBS), which is also a rare condition that increases cancer risk.
- - The case is notable because this specific combination of ETP-LBL and NBS has not been previously reported in medical literature.
- - The authors suggest that the chromosomal instability associated with NBS might elevate the risk of developing ETP-ALL/LBL, paralleling findings that ETP-ALL generally displays greater genomic instability than traditional T-ALL.
Radiosensitivity in a newborn with microcephalia: A case report of Nijmegen breakage syndrome.
Birth Defects Res
May 2024
Department of Medical Genetics, Faculty of Medicine, Zonguldak Bülent Ecevit University Zonguldak, Turkey.
Article Synopsis
- * In a case involving a newborn with microcephaly, researchers discovered increased chromosomal rearrangements and identified a specific deletion in the NBN gene responsible for NBS.
- * The conclusion stresses the importance of assessing newborns with microcephaly for NBS and similar syndromes, particularly regarding the implications of chromosomal instability and radiosensitivity for patient care.
[Research Progress in the Roles of MRE11-RAD50-NBS1 Complex and Human Diseases].
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
April 2024
Women's Hospital,School of Medicine, Zhejiang University,Hangzhou 310006,China.
Article Synopsis
- DNA is prone to damage, particularly double-strand breaks (DSBs), and organisms rely on various repair mechanisms, with homologous recombination (HR) being the most accurate.
- The MRE11-RAD50-NBS1 (MRN) complex is crucial for HR and is conserved across species, with significant findings from recent studies on its role in mammalian DNA repair.
- The review discusses the MRN complex's composition, structure, its involvement in human diseases like ataxia-telangiectasia-like disorder and Nijmegen breakage syndrome, and it highlights mouse models used to study these clinical conditions.
Glucose control during pregnancy in patients with type 1 diabetes correlates with fetal hemodynamics: a prospective longitudinal study.
BMC Pregnancy Childbirth
April 2024
Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Article Synopsis
- - **Context**: Maternal diabetes negatively impacts the development of the fetal cardiovascular system, with an emphasis on the link between maternal glucose control and fetal heart structure/function.
- - **Study Design**: A case-control study with 62 pregnant women with type 1 diabetes and 30 healthy controls assessed fetal heart measures in the second and third trimesters using various ultrasound techniques, while analyzing maternal glucose management over three gestational periods.
- - **Findings**: Fetuses of diabetic mothers showed significant changes (e.g., increased heart dimensions and output) compared to controls, and certain fetal heart metrics were inversely related to poor glucose control and higher hemoglobin levels
Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children.
Blood
May 2024
Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN.
Article Synopsis
- Nijmegen breakage syndrome is linked to biallelic mutations in the NBN gene, increasing the risk of lymphoid cancers, including leukemia for heterozygous carriers.
- A study of 4,325 pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients discovered 25 unique damaging NBN variants, showing a significant increase in frequency compared to noncancer controls.
- Functional assays confirmed 14 of these variants as having severe loss-of-function effects, but carriers of NBN variants had similar survival outcomes as those without such mutations, indicating they can safely undergo standard B-ALL therapies.
Accuracy of unilateral and bilateral gait assessment using a mobile gait analysis system at different walking speeds.
Gait Posture
March 2024
Department of Orthopedic and Trauma Surgery, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Article Synopsis
- Previous research primarily focused on bilateral gait characteristics, but this study aimed to evaluate the accuracy of unilateral gait characteristics using a mobile system at different walking speeds.
- The study included 47 healthy young adults walking on a treadmill at three velocities, comparing data from a traditional instrumented treadmill with that from a mobile gait analysis system.
- Results showed strong correlations in stride length and cadence, but significant errors were found in unilateral parameters, particularly double support duration, prompting questions about the mobile system's validity in detecting gait asymmetries.
Time is the enemy: Negative symptoms are related to even slight differences in the duration of untreated psychosis.
Compr Psychiatry
April 2024
National Institute of Mental Health, Klecany, Czech Republic; 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Article Synopsis
- Negative symptoms in schizophrenia negatively impact social and occupational outcomes, and this study aimed to identify baseline predictors of these symptoms measured four years later in first-episode patients.* -
- The analysis of 77 patients found that the duration of untreated psychosis (DUP) and severity of negative symptoms at the initial visit were significant predictors of later severity, with longer DUP correlating strongly with increased negative symptoms.* -
- The findings emphasize the importance of early intervention in schizophrenia, as prolonged DUP is linked to worsening negative symptoms, highlighting the need for preventive measures in clinical practice.*
Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.
Technol Cancer Res Treat
February 2024
Department of Clinical Laboratory, Fudan University, Shanghai Cancer Center, Shanghai, China.
Article Synopsis
- * The research used various methods to determine how downregulating NBS1 affects cell cycle checkpoints and its relationship with CyclinB, revealing that low NBS1 levels impair DNA repair and activate specific cellular pathways.
- * Findings indicate that reducing NBS1 enhances the sensitivity of ovarian cancer cells to the drug Olaparib by causing cell cycle arrest and suggests that targeting NBS1 could be a viable strategy in treating ovarian cancer.
Neurological involvement in patients with primary immunodeficiency.
Allergol Immunopathol (Madr)
January 2024
Department of Pediatric Immunology and Rheumatology, Bursa Uludag University, Turkey;
Article Synopsis
- - Primary immunodeficiency diseases (PID) are associated with recurrent infections and can significantly impact neurological health, with conditions like Ataxia-Telangiectasia, Nijmegen breakage syndrome, and PNP deficiency demonstrating direct neurological involvement.
- - A study analyzed 108 PID patients and found that the median age for neurological issues was 7 years, with Di George Syndrome and common variable immunodeficiency being the most prevalent.
- - The results revealed that 99% of patients had central nervous system involvement, with cognitive delays, epilepsy, and ataxia being common outcomes; MRI scans of the brain showed abnormalities in 74% of the patients, highlighting various neurological disorders.
Metastasis of ovarian cancer to nasal skin and skin on the trunk: a rare case report.
Front Oncol
October 2023
Department of Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Cutaneous metastases of ovarian cancer are rare and often have poor prognosis. We report a case of a 62-year-old woman with recurrent low-grade serous ovarian cancer, who presented with lung, brain, and multiple skin (nasal and anterior chest wall) metastases approximately six months after the initial diagnosis. In this case, Nijmegen breakage syndrome carrier status caused by RAD50 heterozygous mutation and previous bevacizumab therapy could be the predisposing factor for cutaneous metastases.
View Article and Find Full Text PDFPhosphorylated Hsp27 promotes adriamycin resistance in breast cancer cells through regulating dual phosphorylation of c-Myc.
Cell Signal
December 2023
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China. Electronic address:
Article Synopsis
- Chemotherapy resistance in breast cancer significantly impacts survival rates, with Heat shock protein 27 (Hsp27) implicated in this resistance, though its exact role is not fully understood.
- The study found that overexpression of Hsp27 in adriamycin-resistant breast cancer cells reduced DNA damage and cell death by promoting the stability and import of the c-Myc protein.
- Phosphorylation of Hsp27 during adriamycin treatment shifts it to the nucleus, where it enhances c-Myc levels and activates ATM, indicating Hsp27's crucial role in chemotherapy resistance in breast cancer.
Bone Marrow Failure and Immunodeficiency Associated with Human RAD50 Variants.
J Clin Immunol
November 2023
Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
Article Synopsis
- - The study focuses on a patient with a newly identified RAD50 deficiency that resembles Nijmegen breakage syndrome (NBS), presenting symptoms like bone marrow failure and immunodeficiency, alongside physical and cognitive challenges. - Through whole-exome sequencing, researchers found two variants in the RAD50 gene in the patient, but they noted that although RAD50 protein levels were normal, the ability to respond to DNA damage was significantly impaired. - The results highlight the crucial role of RAD50 in bone marrow and immune function, suggesting that RAD50 deficiency can lead to unique immune disorders marked by bone marrow issues and B-cell deficiency.
Plasma Circulating Cell-free DNA in Advanced Hepatocellular Carcinoma Patients Treated With Radiation Therapy.
In Vivo
November 2023
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea;
Article Synopsis
- The study aimed to identify effective biomarkers for predicting treatment response in patients with hepatocellular carcinoma (HCC) undergoing radiation therapy (RT) by evaluating circulating cell-free DNA (cfDNA).
- A total of 37 patients were monitored before and after RT, measuring cfDNA genomic copy number variations (CNVs), which helped determine potential treatment outcomes.
- Results showed that the I-score derived from cfDNA was a strong predictive marker for progression-free survival, indicating its potential as a biomarker for assessing the efficacy of RT in advanced HCC.
Germline Genetic Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.
Res Sq
July 2023
Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Article Synopsis
- Biallelic mutations in the DNA repair gene are linked to Nijmegen Breakage Syndrome and can increase the risk of certain cancers, including lymphoid malignancies in children.
- A study found 25 potentially harmful genetic variants in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL), indicating a higher occurrence compared to non-cancer controls.
- Functional testing confirmed 14 variants as pathogenic, showing severe loss of function, but patients carrying one of these variants had similar survival rates to those without the variants, suggesting they can undergo standard B-ALL treatment safely.