Article
Genetics & Heredity
Sara Biagiotti, Ambra Barone, Mattia Paolo Aliano, Giulia Federici, Marco Malatesta, Caterina Caputi, Silvia Soddu, Vincenzo Leuzzi, Luciana Chessa, Mauro Magnani
Summary: Most ATM variants associated with Ataxia Telangiectasia are classified as variants with uncertain significance. This study focused on a specific ATM variant found in Lebanese brothers, revealing it to be pathogenic even though it causes an atypical phenotype. Dexamethasone showed therapeutic potential on this and possibly other missense ATM variants.
FRONTIERS IN GENETICS
(2021)
Article
Environmental Sciences
Robert B. Hood, Metrecia L. Terrell, Alicia K. Smith, Sarah Curtis, Karen Conneely, Melanie Pearson, Hillary Barton, Dana Boyd Barr, Elizabeth M. Marder, Michele Marcus
Summary: This study investigated the widespread contamination of polybrominated biphenyl (PBB), a flame retardant, into the food system in Michigan in the 1970's. It found that PBB continues to be detected in Michiganders' blood some forty years later. The study estimated the elimination rate and half-life of PBB, providing clues on how to hasten its elimination from the human body.
ENVIRONMENTAL RESEARCH
(2023)
Article
Rheumatology
Alexis F. Guedon, Fabrice Carrat, Luc Mouthon, David Launay, Benjamin Chaigne, Gregory Pugnet, Jean-Christophe Lega, Arnaud Hot, Vincent Cottin, Christian Agard, Yannick Allanore, Anne-Laure Fauchais, Patrick Jego, Robin Dhote, Thomas Papo, Emmanuel Chatelus, Bernard Bonnotte, Jean-Emmanuel Khan, Elisabeth Diot, Boris Bienvenu, Nadine Magy-Bertrand, Viviane Queyrel, Alain Le Quellec, Pierre Kieffer, Zahir Amoura, Jean-Robert Harle, Jean-Baptiste Gaultier, Marie-Helene Balquet, Denis Wahl, Olivier Lidove, Olivier Fain, Arsene Mekinian, Eric Hachulla, Sebastien Riviere
Summary: This study investigated the prevalence and prognostic burden of heart involvement in SSc patients. The results showed that SSc-related cardiac involvement was associated with an increased risk of death, and diffuse SSc subtype and female sex were identified as risk factors. Further analysis should assess the potential impact of treatment on various cardiac outcomes.
Review
Biochemistry & Molecular Biology
Goutham Narayanan Subramanian, Abrey Jie Yeo, Magtouf Hnaidi Gatei, David John Coman, Martin Francis Lavin
Summary: The ATM protein kinase has diverse functions in the cell, including protecting DNA, maintaining cellular homeostasis, and safeguarding against external and internal damage.
Article
Biology
Harvey Perez, May F. Abdallah, Jose Chavira, Angelina S. Norris, Martin T. Egeland, Karen L. Vo, Callan L. Buechsenschuetz, Valentina Sanghez, Jeannie L. Kim, Molly Pind, Kotoka Nakamura, Geoffrey G. Hicks, Richard A. Gatti, Joaquin Madrenas, Michelina Iacovino, Peter J. McKinnon, Paul J. Mathews
Summary: By introducing null mutations in both the Atm and Aptx genes in mice, researchers have created a novel mouse model that exhibits progressively severe ataxic phenotype and cerebellar molecular layer atrophy. The perturbations significantly alter the biophysical properties of cerebellar Purkinje neurons and their neural activity, correlating with cerebellar atrophy and ataxia over the animal's first year of life. Additionally, the double mutant mice also show a predisposition to cancer and immune abnormalities, resembling symptoms of A-T.
Article
Biochemistry & Molecular Biology
Jakub Czarny, Marta Andrzejewska, Olga Zajac-Spychala, Elzbieta Latos-Grazynska, Agata Pastorczak, Kamila Wypyszczak, Aleksandra Szczawinska-Poplonyk, Izabela Niewiadomska-Wojnalowicz, Agnieszka Wziatek, Patrycja Marciniak-Stepak, Michal Dopierala, Jadwiga Maldyk, Katarzyna Jonczyk-Potoczna, Katarzyna Derwich
Summary: Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by DNA repair defect, chromosomal instability, and hypersensitivity to radiation. Successful clinical management of patients with AT is challenging due to poor treatment response, high toxicity, and the need to avoid radiation exposure. This case report describes a 7-year-old female patient with AT and LBCL with IRF4 rearrangement who achieved a favorable outcome through treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Venturina Stagni, Alessandra Ferri, Claudia Cirotti, Daniela Barila
Summary: There is a strong interplay between autophagy and genomic stability, with recent evidence linking DNA Damage Response (DDR) and autophagy in influencing cell fate. ATM kinase plays a crucial role in balancing senescence and apoptosis in response to stimuli, and its aberrant deregulation is linked to the development of pathologies like cancer and neurodegeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Rudel A. Saunders, Thomas F. Michniacki, Courtney Hames, Hilary A. Moale, Carol Wilke, Molly E. Kuo, Johnathan Nguyen, Andrea J. Hartlerode, Bethany B. Moore, JoAnn M. Sekiguchi
Summary: Ataxia-telangiectasia (A-T) is a multisystem disorder with lung complications as a major cause of mortality. This study demonstrates the significant role of ATM-deficient immune cells in causing lung pathologies in A-T, and suggests that targeted inhibition of aberrant inflammatory responses could be a viable therapeutic strategy for A-T lung disease.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Maria Likhatcheva, Roben G. Gieling, James A. L. Brown, Constantinos Demonacos, Kaye J. Williams
Summary: Genotoxic stress can activate the ATM kinase, with potential involvement of Suv39H1 and Tip60 in ATM activation under hypoxic conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Genetics & Heredity
B. Dalmasso, L. Pastorino, V Nathan, N. N. Shah, J. M. Palmer, M. Howlie, P. A. Johansson, N. D. Freedman, B. D. Carter, L. Beane-Freeman, B. Hicks, A. Molven, H. Helgadottir, A. Sankar, H. Tsao, A. J. Stratigos, P. Helsing, R. Van Doorn, N. A. Gruis, M. Visser, K. A. W. Wadt, G. Mann, E. A. Holland, E. Nagore, M. Potrony, S. Puig, C. Menin, K. Peris, M. C. Fargnoli, D. Calista, N. Soufir, M. Harland, T. Bishop, P. A. Kanetsky, D. E. Elder, V Andreotti, I Vanni, W. Bruno, V Hoiom, M. A. Tucker, X. R. Yang, P. A. Andresen, D. J. Adams, M. T. Landi, N. K. Hayward, A. M. Goldstein, P. Ghiorzo
Summary: This study supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Boxun Zhao, Minh A. Nguyen, Sijae Woo, Jinkuk Kim, Timothy W. Yu, Eunjung Alice Lee
Summary: This study conducted retroelement profiling on whole-genome sequencing data from 237 individuals with ataxia telangiectasia (A-T), and found retroelement insertions in the ATM gene in 15 individuals. Most of the insertions were located in noncoding regions, and 12 intronic insertions led to ATM loss of function. The study also presented proof-of-concept antisense oligonucleotides that can suppress cryptic exonization caused by deep intronic retroelement insertion.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Immunology
Geraldine Blanchard-Rohner, Anna Peirolo, Ludivine Coulon, Christian Korff, Judit Horvath, Pierre R. Burkhard, Fabienne Gumy-Pause, Emmanuelle Ranza, Peter Jandus, Harpreet Dibra, Alexander Malcolm R. Taylor, Joel Fluss
Summary: Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder characterized by various symptoms. This study presents a case series highlighting the phenotypic variability of A-T and emphasizes the importance of early diagnosis of variant A-T and classical A-T.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Mark Yates, Joanna M. Ledingham, Paul Amlani Hatcher, Maryam Adas, Sasha Hewitt, Sam Bartlett-Pestell, Sanketh Rampes, Sam Norton, James B. Galloway
Summary: Gender, socioeconomic position, and ethnicity are predictors of disease activity in early inflammatory arthritis patients. Patients with lower socioeconomic positions tend to have higher disease activity levels, while Black, Asian, and Minority Ethnic patients have lower odds of remission after a certain period of time. Additional data is needed to further assess area-level variation in disease activity.
Article
Clinical Neurology
Ilaria Di Donato, Antonio Gallo, Ivana Ricca, Nicola Fini, Gabriella Silvestri, Fiorella Gurrieri, Mario Cirillo, Alfonso Cerase, Gemma Natale, Federica Matrone, Vittorio Riso, Mariarosa Anna Beatrice Melone, Alessandra Tessa, Giovanna De Michele, Antonio Federico, Alessandro Filla, Maria Teresa Dotti, Filippo Maria Santorelli
Summary: Mutations in the POLR3A gene exhibit high phenotypic heterogeneity, with manifestations ranging from severe diseases to milder symptoms. Late-onset spastic ataxia without hypomyelinating leukodystrophy has been linked to the c.1909 + 22G > A mutation in POLR3A. This cohort of patients with POLR3A-related disorders showed various neurological symptoms, with one patient displaying features not previously reported in association with late-onset POLR3A-related disorders.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Rebecca Presterud, Wei Hai Deng, Anna Berit Wennerstrom, Trudy Burgers, Bharat Gajera, Kirsten Mattsson, Agnes Solberg, Evandro F. Fang, Anni I. Nieminen, Asbjorg Stray-Pedersen, Hilde Nilsen
Summary: Long-term supplementation of nicotinamide riboside (NR) appears to be safe and well tolerated in patients with ataxia telangiectasia (A-T), and it improves motor coordination and eye movements.
MOVEMENT DISORDERS
(2023)