Article
Cell Biology
Clement Crochemore, Claudia Chica, Paolo Garagnani, Giovanna Lattanzi, Steve Horvath, Alain Sarasin, Claudio Franceschi, Maria Giulia Bacalini, Miria Ricchetti
Summary: Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein. CS displays a progeroid and neurodegenerative phenotype, and differential analysis of DNA methylation (DNAm) revealed a CS-specific epigenomic signature enriched in developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. CS also exhibited epigenetic hallmarks of accelerated ageing, including hypomethylation of Alu sequences and increased biological age compared to healthy and UVSS cells.
Article
Cell Biology
Maria B. Birkisdottir, Dick Jaarsma, Renata M. C. Brandt, Sander Barnhoorn, Nicole van Vliet, Sandra Imholz, Conny T. van Oostrom, Bhawani Nagarajah, Eliana Portilla Fernandez, Anton J. M. Roks, Ype Elgersma, Harry van Steeg, Jose A. Ferreira, Jeroen L. A. Pennings, Jan H. J. Hoeijmakers, Wilbert P. Vermeij, Martijn E. T. Dolle
Summary: Experimental results show that although dietary restriction and rapamycin can extend the lifespan of some organisms, rapamycin cannot increase the lifespan and healthspan of progeroid DNA repair-deficient mice like dietary restriction does.
Article
Neurosciences
Qiongling Peng, Yan Zhang, Binqiang Xian, Lianying Wu, Jianying Ding, Wuwu Ding, Xin Zhang, Bilan Ding, Ding Li, Jin Wu, Xiaowu Hu, Guanting Lu
Summary: Wiedemann-Rautenstrauch syndrome is a rare autosomal recessive neonatal disorder. This study reports a case of a female patient with growth retardation, neurocutaneous syndrome, and anemia, and identifies compound mutations in the POLR3A and FANCA genes. The study also reveals that these mutations may affect gene splicing and lead to the development of WDRTS.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Pediatrics
Shao-Wen Wu, Lin Li, Fan Feng, Li Wang, Yuan-Yuan Kong, Xiao-Wei Liu, Chenghong Yin
Summary: In this study, a novel WRS-associated gene, POLR3B, was identified, expanding the mutational and phenotypic spectra of POLR3B. Whole-exome sequencing was found to be useful for detecting rare disease-related genetic variants.
ITALIAN JOURNAL OF PEDIATRICS
(2021)
Article
Health Care Sciences & Services
Hsiang-Yu Lin, Chung-Lin Lee, Sisca Fran, Ru-Yi Tu, Ya-Hui Chang, Dau-Ming Niu, Chia-Ying Chang, Pao Chin Chiu, Yen-Yin Chou, Hui-Pin Hsiao, Chia-Feng Yang, Meng-Che Tsai, Tzu-Hung Chu, Chih-Kuang Chuang, Shuan-Pei Lin
Summary: Lower IC2 methylation and higher IC1 methylation levels were associated with greater disease severity in clinically diagnosed BWS patients. The methylation levels of IC2 were correlated with specific clinical manifestations and birth characteristics, enhancing the detection of BWS and improving genetic counseling and medical care for these patients.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Medicine, General & Internal
Andrew N. J. Tutt, Judy E. Garber, Bella Kaufman, Giuseppe Viale, Debora Fumagalli, Priya Rastogi, Richard D. Gelber, Evandro de Azambuja, Anitra Fielding, Judith Balmana, Susan M. Domchek, Karen A. Gelmon, Simon J. Hollingsworth, Larissa A. Korde, Barbro Linderholm, Hanna Bandos, E. Senkus, Jennifer M. Suga, Z. Shao, Andrew W. Pippas, Zbigniew Nowecki, Tomasz Huzarski, Patricia A. Ganz, Peter C. Lucas, Nigel Baker, Sibylle Loibl, Robin McConnell, Martine Piccart, Rita Schmutzler, Guenther G. Steger, Joseph P. Costantino, Amal Arahmani, Norman Wolmark, Eleanor McFadden, Vassiliki Karantza, Sunil R. Lakhani, Greg Yothers, Christine Campbell, Charles E. Geyer
Summary: In patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than placebo. Olaparib had limited effects on global patient-reported quality of life.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Cell Biology
Yang Wang, Tianyu Yu, Yi Han, Yazhi He, Yiran Song, Leiming Guo, Liwei An, Chunying Yang, Feng Wang
Summary: This study reveals the key regulatory role of Mad2 phosphorylation in checkpoint defects and DNA damage repair in ATM-deficient cells. ATM negatively regulates the phosphorylation of Mad2, causing decreased DNA damage repair capacity and resistance to cancer cell radiotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Purvi Majethia, Katta Mohan Girisha
Summary: Wiedemann-Rautenstrauch syndrome is a rare genetic disorder characterized by growth retardation, lipoatrophy, a distinctive face, sparse scalp hair, and dental anomalies. It is rarely reported and has been found in an Indian patient as well.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Cell Biology
Martine de Boer, Maaike te Lintel Hekkert, Jiang Chang, Bibi S. van Thiel, Leonie Martens, Maxime M. Bos, Marion G. J. de Kleijnen, Yanto Ridwan, Yanti Octavia, Elza D. van Deel, Lau A. Blonden, Renata M. C. Brandt, Sander Barnhoorn, Paula K. Bautista-Nino, Ilona Krabbendam-Peters, Rianne Wolswinkel, Banafsheh Arshi, Mohsen Ghanbari, Christian Kupatt, Leon J. de Windt, A. H. Jan Danser, Ingrid van der Pluijm, Carol Ann Remme, Monika Stoll, Joris Pothof, Anton J. M. Roks, Maryam Kavousi, Jeroen Essers, Jolanda van der Velden, Jan H. J. Hoeijmakers, Dirk J. Duncker
Summary: Heart failure has become an epidemic in an aging population, and DNA damage is believed to play a role in its development. This study found that impaired DNA repair in cardiomyocytes leads to early onset of heart failure, with increased oxidative stress, fibrosis, and apoptosis. The findings suggest that DNA damage could be a potential therapeutic target for heart failure.
Article
Biochemistry & Molecular Biology
Aidin Foroutan, Sadegheh Haghshenas, Pratibha Bhai, Michael A. Levy, Jennifer Kerkhof, Haley McConkey, Marcello Niceta, Andrea Ciolfi, Lucia Pedace, Evelina Miele, David Genevieve, Solveig Heide, Marielle Alders, Giuseppe Zampino, Giuseppe Merla, Melanie Fradin, Eric Bieth, Dominique Bonneau, Klaus Dieterich, Patricia Fergelot, Elise Schaefer, Laurence Faivre, Antonio Vitobello, Silvia Maitz, Rita Fischetto, Cristina Gervasini, Maria Piccione, Ingrid van de Laar, Marco Tartaglia, Bekim Sadikovic, Anne-Sophie Lebre
Summary: Wiedemann-Steiner syndrome is a Mendelian syndromic intellectual disability condition associated with pathogenic variants in the KMT2A gene. The clinical features of this syndrome can be variable, making interpretation and classification of rare KMT2A variants challenging. By assessing the genome-wide DNA methylation profiles, a unique DNA methylation episignature was identified as a molecular biomarker for WDSTS, enabling classification of variants and confirmation of diagnosis in patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Benjamin Klein, Claudia Guenther
Summary: Type I interferons play a crucial role in autoimmune disorders and interferonopathies, but uncontrolled activation may lead to autoinflammation and autoimmunity. Various mechanisms promote IFN secretion upon increased DNA damage, which is similar to the features seen in hereditary cutaneous DNA damage syndromes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Jamie Lee, Joshua Zhang, Maeve Flanagan, Julian A. Martinez, Christopher Cunniff, Nicole Kucine, Ake T. Lu, Amin Haghani, Juozas Gordevicius, Steve Horvath, Vivian Y. Chang
Summary: Bloom syndrome (BSyn) is caused by variants in the BLM gene and manifests as poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased cancer risk, particularly leukemias. Our study reveals accelerated epigenetic aging in BSyn patients compared to carriers, as evidenced by multiple measures in blood lymphocytes. Additionally, homozygous Blm mice exhibit accelerated methylation age in various tissues according to the brain methylation clock. Overall, Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and significant impact on CpG methylation levels.
Article
Cell Biology
Jong-Hyuk Lee, Raghavendra A. Shamanna, Tomasz Kulikowicz, Nima Borhan Fakouri, Edward W. Kim, Louise S. Christiansen, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability caused by WRN protein deficiency. The phosphorylation of WRN by CDK2 on serine residue 426 is critical for WRN to choose between non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. The phosphorylation stabilizes WRN's affinity for RPA and enhances its role in long-range resection, a crucial step for HR.
Article
Multidisciplinary Sciences
Magdalena M. Kordon, Sarah Arron, James E. Cleaver, Vladimir Bezrookove, Deneb Karentz, Brian Lu, Eli Perr, Darwin Chang, Thoru Pederson
Summary: The UVSSA protein is involved in transcription-coupled repair and its mutations can cause mild photosensitive syndrome. In this study, the UVSSA gene was disrupted in HEK293 cells, resulting in sensitivity to transcription-blocking lesions. The findings contribute to the understanding of DNA diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Francesco Cecere, Laura Pignata, Bruno Hay Mele, Abu Saadat, Emilia D'Angelo, Orazio Palumbo, Pietro Palumbo, Massimo Carella, Gioacchino Scarano, Giovanni Battista Rossi, Claudia Angelini, Angela Sparago, Flavia Cerrato, Andrea Riccio
Summary: This study reports a case of early-onset colorectal cancer (EO-CRC) in a 27-year-old woman with Beckwith-Wiedemann syndrome (BWSp). Genetic and epigenetic analysis revealed the presence of genetic and epigenetic variations that may be associated with the development of EO-CRC.