Article
Oncology
Nancy Alnassar, Malgorzata Borczyk, Georgia Tsagkogeorga, Michal Korostynski, Namshik Han, Dariusz C. Gorecki
Summary: Mutations in the DMD gene cause Duchenne muscular dystrophy (DMD), but recent research shows that reduced DMD expression is also associated with various malignancies. The downregulation of DMD in tumors is correlated with reduced patient survival and tumor stage. These findings challenge the current understanding of dystrophin expression and suggest a broader significance of the DMD gene beyond DMD.
Review
Oncology
Leanne Jones, Michael Naidoo, Lee R. Machado, Karen Anthony
Summary: Mutation of the DMD gene causes muscular dystrophies, but it is also implicated in the development of major cancer types. Disruption of the balance of DMD gene products in cancer may play a key role in tumorigenesis. Further study into the potential role of DMD gene products in cancer is needed to develop new therapeutics.
Article
Genetics & Heredity
Mariko Okubo, Satoru Noguchi, Tomonari Awaya, Motoyasu Hosokawa, Nobue Tsukui, Megumu Ogawa, Shinichiro Hayashi, Hirofumi Komaki, Madoka Mori-Yoshimura, Yasushi Oya, Yuji Takahashi, Tetsuhiro Fukuyama, Michinori Funato, Yousuke Hosokawa, Satoru Kinoshita, Tsuyoshi Matsumura, Sadao Nakamura, Azusa Oshiro, Hiroshi Terashima, Tetsuro Nagasawa, Tatsuharu Sato, Yumi Shimada, Yasuko Tokita, Masatoshi Hagiwara, Katsuhisa Ogata, Ichizo Nishino
Summary: Dystrophinopathy is a disease caused by alterations in the DMD gene. In this study, a combined laboratory and computational analysis approach was used to identify disease-causing genomic variants and regulatory mechanisms underlying abnormal DMD transcript generation in genetically undiagnosed patients. Abnormal DMD transcripts were detected in the majority of cases, with exonization of intronic sequences, exon skipping, aberrant splicing, polyadenylation, and transcription termination identified as the underlying mechanisms. The findings of this study have important implications for therapeutic options for patients with Dystrophinopathy.
Article
Genetics & Heredity
Xinguo Lu, Chunxi Han, Jiahui Mai, Xianping Jiang, Jianxiang Liao, Yanqi Hou, Di Cui
Summary: This study identified three novel and one reported intronic mutations that can lead to DMD/BMD. The combination of WES and cDNA-based methods is necessary to detect variants in the large and complex DMD gene.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Esra Erkut, Toshifumi Yokota
Summary: DMD is a common neuromuscular disorder and CRISPR gene editing holds promise as a therapeutic approach. However, further research is needed to ensure its safety and accuracy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Cedric Happi Mbakam, Gabriel Lamothe, Guillaume Tremblay, Jacques P. Tremblay
Summary: The discovery of CRISPR-Cas system has brought new possibilities in precision medicine, particularly in the correction of Duchenne muscular dystrophy mutations. However, there are challenges to be addressed before its clinical application, such as off-target editing, efficient delivery, immune response, and vector issues.
Review
Biochemistry & Molecular Biology
Binyamin Eisen, Ofer Binah
Summary: Duchenne muscular dystrophy (DMD) is a degenerative disease caused by mutations in the dystrophin gene, resulting in death by the end of the third decade of life. Cardiac involvement has become an increasing cause of mortality in recent years. Extensive research has been conducted using DMD animal models, but differences between these models and human DMD pose a challenge. The development of somatic cell reprogramming technology has provided a potentially endless pool of human cells for research, with hiPSCs offering patient-specific cells and the possibility of regenerative medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Tina Donandt, Stefan Hintze, Sabine Krause, Eckhard Wolf, Benedikt Schoser, Maggie C. Walter, Peter Meinke
Summary: Duchenne muscular dystrophy (DMD) is a common genetic disease in childhood, but there is no curative treatment yet. We established DMD pig models and an in vitro model for testing new therapies. This has significant implications for minimizing the use of live animals and supporting the 3R principle.
Review
Ophthalmology
Mirella Telles Salgueiro Barboni, Anneka Joachimsthaler, Michel J. Roux, Zoltan Zsolt Nagy, Dora Fix Ventura, Alvaro Rendon, Jan Kremers, Cyrille Vaillend
Summary: Duchenne muscular dystrophy (DMD) is a genetic disorder that mainly affects males and causes early-onset muscle degeneration, leading to reduced quality of life and decreased life expectancy. DMD patients may also experience retinopathy, vision abnormalities, and other retinal complications. The loss of dystrophins in the retina disrupts synaptic transmission, ionic balance, and vascular integrity, but the specific functions of retinal dystrophins remain unclear. This review highlights the current knowledge on dystrophin expression, the potential molecular and physiological properties of retinal dystrophins, and the clinical implications for DMD patients and mouse models.
PROGRESS IN RETINAL AND EYE RESEARCH
(2023)
Article
Physiology
Jose Manuel Pioner, Lorenzo Santini, Chiara Palandri, Marianna Langione, Bruno Grandinetti, Silvia Querceto, Daniele Martella, Costanza Mazzantini, Beatrice Scellini, Lucrezia Giammarino, Flavia Lupi, Francesco Mazzarotto, Aoife Gowran, Davide Rovina, Rosaria Santoro, Giulio Pompilio, Chiara Tesi, Camilla Parmeggiani, Michael Regnier, Elisabetta Cerbai, David L. Mack, Corrado Poggesi, Cecilia Ferrantini, Raffaele Coppini
Summary: Cardiomyocytes differentiated from human induced Pluripotent Stem Cells (hiPSC- CMs) are a unique source for studying inherited cardiomyopathies. Calcium handling abnormalities, especially the contribution of the sarcoplasmic reticulum (SR) to Ca release, play a crucial role in cardiomyocyte dysfunction. Dystrophin-deficient cardiomyocytes display impaired calcium homeostasis in response to increases in extracellular matrix stiffness.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alicja Starosta, Patryk Konieczny
Summary: DMD is a devastating X-linked disease characterized by progressive skeletal muscle wasting and heart dysfunction. Therapeutic strategies involving epigenetic modifications to modulate signal pathways have emerged as promising approaches. Taking a systemic view of DMD as a disease affecting muscle fibers and communication between different cell types may lead to holistic treatments that restore proper signal transmission and gene expression.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Clinical Neurology
Mengyuan Chang, Yong Cai, Zihui Gao, Xin Chen, Boya Liu, Cheng Zhang, Weiran Yu, Qianqian Cao, Yuntian Shen, Xinlei Yao, Xiaoyang Chen, Hualin Sun
Summary: Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease, characterized by deterioration of skeletal muscle and loss of mobility. The failure of respiratory and cardiac muscles is the main cause of premature death in most DMD patients. Dystrophin deficiency, caused by mutations in the dystrophin gene, plays a crucial role in the pathogenesis of DMD, leading to muscle cell damage and dysfunction.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Kate Maresh, Andriani Papageorgiou, Deborah Ridout, Neil A. Harrison, William Mandy, David Skuse, Francesco Muntoni
Summary: Duchenne muscular dystrophy (DMD) patients, in addition to muscle loss, also experience intellectual disability and neurobehavioral co-morbidities. This study shows that boys with DMD exhibit increased startle responses to threat, similar to a DMD mouse model, and these responses normalize with dystrophin restoration.
Article
Multidisciplinary Sciences
Maria Sofia Falzarano, Martina Mietto, Fernanda Fortunato, Marianna Farne, Fernanda Martini, Pierpaolo Ala, Rita Selvatici, Francesco Muntoni, Alessandra Ferlini
Summary: This study investigated the transcription dynamics and spatial localization of the dystrophin (DMD) gene in DMD patients. The results showed significantly reduced DMD mRNA amount in the patients' cells and muscle biopsies, with a shift towards localization in the nuclei. This abnormal compartmentalization of mutant DMD mRNA contributes to the poor abundance and availability of dystrophin messenger in the cytoplasm.
SCIENTIFIC REPORTS
(2023)
Article
Health Care Sciences & Services
Saeed Anwar, Merry He, Kenji Rowel Q. Lim, Rika Maruyama, Toshifumi Yokota
Summary: This study found that five exons are associated with significantly milder phenotypes, while most exon skip-equivalent in-frame deletions were associated with a significantly milder phenotype compared to corresponding exon skip-amenable out-of-frame mutations. This highlights the importance of genotype-phenotype correlation studies in the rational design of exon-skipping therapies.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Pediatrics
Sachiyo Fukushima, Nobuto Nakanishi, Kazumichi Fujioka, Kenichi Suga, Taku Shirakawa, Kayo Osawa, Kanako Hara, Rie Tsutsumi, Maki Urushihara, Ryuji Nakagawa, Hiroyuki Awano, Jun Oto, Hiroshi Sakaue, Kazumoto Iijima, Masafumi Matsuo
Summary: This study investigated the changes in urinary titin N-fragment levels in infants with postmenstrual age, revealing an exponential decline with postmenstrual age and a significant increase in catabolic state in preterm infants.
PEDIATRIC RESEARCH
(2022)
Article
Rheumatology
Kenichi Uto, Koji Ueda, Takaichi Okano, Kengo Akashi, Soshi Takahashi, Yuji Nakamachi, Takamitsu Imanishi, Hiroyuki Awano, Akio Morinobu, Seiji Kawano, Jun Saegusa
Summary: This study identified the enrichment of plexin D1 in serum EVs of PM/DM patients, developed a specific EV sandwich ELISA, and found that levels of plexin D1(+) EVs were significantly increased in PM/DM patients, especially in those with muscle pain or weakness. The serum levels of plexin D1(+) EVs were significantly correlated with aldolase, white blood cells, neutrophils, and platelets in PM/DM patients, and decreased significantly in patients with PM/DM in clinical remission after treatment.
Article
Clinical Neurology
Hiroshi Yamaguchi, Hiroyuki Awano, Tetsushi Yamamoto, Yoshinori Nambu, Kazumoto Iijima
Summary: This study reveals that elevated serum levels of cTnI are more common and severe in DMD patients, suggesting it may represent an early phase of cardiomyopathy progression. The ACTN3 XX genotype may be a risk factor for early myocardial injury.
Article
Transplantation
Nana Sakakibara, Takeshi Ijuin, Tomoko Horinouchi, Tomohiko Yamamura, China Nagano, Eri Okada, Shinya Ishiko, Yuya Aoto, Rini Rossanti, Takeshi Ninchoji, Hiroyuki Awano, Hiroaki Nagase, Shogo Minamikawa, Ryojiro Tanaka, Takeshi Matsuyama, Koji Nagatani, Koichi Kamei, Kumiko Jinnouchi, Yasufumi Ohtsuka, Masafumi Oka, Yoshinori Araki, Toju Tanaka, Mari S. Harada, Toru Igarashi, Hikaru Kitahara, Naoya Morisada, Shun-Ichi Nakamura, Taro Okada, Kazumoto Iijima, Kandai Nozu
Summary: This study elucidated the molecular mechanism underlying the different phenotypes in OCRL-related diseases, revealing that the functional OCRL isoform translated starting at exon 8 is associated with this mechanism.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Urology & Nephrology
Yuya Aoto, Tomoko Horinouchi, Tomohiko Yamamura, Atsushi Kondo, Sadayuki Nagai, Shinya Ishiko, Eri Okada, Rini Rossanti, Nana Sakakibara, China Nagano, Hiroyuki Awano, Hiroaki Nagase, Yuko Shima, Koichi Nakanishi, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
Summary: This study revealed that most single-base substitutions at the last nucleotide position of COL4A5 exons result in splicing variants rather than missense variants, leading to more severe phenotypes.
KIDNEY INTERNATIONAL REPORTS
(2022)
Review
Medicine, Research & Experimental
Min Yang, Hiroyuki Awano, Satoru Tanaka, Walter Toro, Su Zhang, Omar Dabbous, Ataru Igarashi
Summary: This systematic literature review highlights the need for more up-to-date and methodologically rigorous clinical, health-related quality of life (HRQOL), and economic data to assess the relative clinical and economic effectiveness of spinal muscular atrophy (SMA) treatments. The review also reveals that untreated SMA is associated with significant humanistic and economic burden.
ADVANCES IN THERAPY
(2022)
Article
Nanoscience & Nanotechnology
Satoshi Sumi, Hiroyuki Awano, Junji Tominaga
Summary: In this study, we report the experimental results of a [GeTe/Sb2Te3] superlattice with a topologically protected spin diffusion length exceeding 100 μm at room temperature. By using a TbFeCo film for laser-induced spin injection into the superlattice, we successfully obtained spin injection signals between TbFeCo and Pt bars without electric current. This research provides a useful method for future low-energy spintronics devices.
Article
Genetics & Heredity
Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Hisahide Nishio, Kentaro Okamoto, Hiroyuki Awano, Toshio Saito, Yasuhiro Takeshima, Masakazu Shinohara
Summary: This study examined the effects of high-concentration ASOs and combining two ASOs on splicing efficiency using SMA fibroblasts. The results showed that low or intermediate concentrations of ASOs had better splicing efficiency, while high concentrations of ASOs resulted in the creation of a cryptic exon.
Article
Genetics & Heredity
Chie Fujisawa, Hiroko Kodama, Yasuhiro Sato, Masakazu Mimaki, Mariko Yagi, Hiroyuki Awano, Muneaki Matsuo, Haruo Shintaku, Sayaka Yoshida, Masaki Takayanagi, Mitsuru Kubota, Akihito Takahashi, Yoshikiyo Akasaka
Summary: Menkes disease is a genetic disorder caused by mutations in ATP7A, resulting in severe neurological and connective tissue disorders. Early diagnosis and treatment can alleviate neurological disturbances, but diagnosing MD based on early symptoms is challenging. Therefore, prioritizing newborn screening for MD is necessary.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Genetics & Heredity
Rini Rossanti, Tomoko Horinouchi, Nana Sakakibara, Tomohiko Yamamura, China Nagano, Shinya Ishiko, Yuya Aoto, Atsushi Kondo, Sadayuki Nagai, Hiroyuki Awano, Hiroaki Nagase, Masafumi Matsuo, Kazumoto Iijima, Kandai Nozu
Summary: In this study, deep intronic variant screening was performed on 13 patients with suspected Gitelman syndrome who carried one mutated allele, and a pathogenic deep intronic variant associated with the disease was identified. This suggests that deep intronic variants partially explain the presence of monoallelic variants in Gitelman syndrome patients.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Physics, Multidisciplinary
Kei Matsumoto, Pham Van Thach, Satoshi Sumi, Sina Ranjbar, Kenji Tanabe, Hiroyuki Awano, Shihao Wang, Takayuki Ishibashi, Shin Saito
Summary: The spin Hall effect, Dzyaloshinskii-Moriya interaction, Rashba effect, etc. are crucial effects for the development of spin electronics, with most studies focused on the frequency domain rather than the energy domain of light. The permittivity tensors in hetero-structured films show different characteristics, indicating the influence of broken spatial inversion symmetry.
FRONTIERS IN PHYSICS
(2022)
Article
Genetics & Heredity
Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hiroyuki Awano
Summary: Spinal muscular atrophy is a common and devastating neuromuscular disorder. Newborn screening can enable early diagnosis, although treatment in the pre-symptomatic stage is not always possible.
Review
Virology
Abdul Qawee Rani, Dilber Nurmemet, Joseph Liffick, Anam Khan, Darrion Mitchell, Jenny Li, Bo Zhao, Xuefeng Liu
Summary: Oncogenic viruses are linked to around 20% of human cancers, but current cell models have limitations in studying viral life cycle and cancer initiation. There is a need for reliable human physiological cell models. Conditional cell reprogramming (CCR) is a rapid and robust system that can establish cells from minimally invasive specimens and preserve their lineage functions.
Review
Chemistry, Analytical
Abdul Qawee Rani, Bo Zhu, Hiroshi Ueda, Tetsuya Kitaguchi
Summary: Homogeneous immunosensors combine the advantages of biosensors and immunoassays, offering speed, high sensitivity, and accuracy. They have seen rapid development in recent years and provide a cost-effective alternative technology with rapidity, sensitivity, and user-friendliness, which has been widely applied. This review introduces current trends in immunosensor development, particularly fluorescent and bioluminescent immunosensors, highlighting their advantages, improvements, and key approaches to address limitations.
Article
Biochemistry & Molecular Biology
Taku Shirakawa, Ayumu Ikushima, Nobuhiro Maruyama, Yoshinori Nambu, Hiroyuki Awano, Kayo Osawa, Kei Nirasawa, Yoichi Negishi, Hisahide Nishio, Shoji Fukushima, Masafumi Matsuo
Summary: The mdx mouse is a model of DMD and is used widely in preclinical studies, but their muscle strength phenotypes are milder than in humans. The development of a highly sensitive ELISA kit to measure titin N-terminal fragment levels in mouse urine has been awaited. This study developed a sandwich ELISA kit to measure titin N-terminal fragment levels in mouse urine and found that the concentrations were significantly higher in mdx mice compared to normal mice.
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
(2022)