Review
Genetics & Heredity
Pitcha Chompoopong, Margherita Milone
Summary: GDP-mannose pyrophosphorylase B (GMPPB) is a cytoplasmic protein that catalyzes the formation of GDP-mannose. Impaired GMPPB function leads to alpha-dystroglycan (alpha-DG) disruptions, causing dystroglycanopathy. GMPPB-related disorders are inherited in an autosomal recessive manner and can manifest as severe congenital muscular dystrophy (CMD), limb-girdle muscular dystrophy (LGMD), or recurrent rhabdomyolysis. Mutations in GMPPB can also affect neuromuscular transmission and cause congenital myasthenic syndrome. The unique feature of GMPPB-related disorders is the impairment of neuromuscular transmission.
Article
Medicine, General & Internal
Mi Yang, Ru-Xin Xing
Summary: Congenital muscular dystrophy (CMD) is a genetically heterogeneous group of muscle disorders. This study identified CRPPA gene mutations in a Chinese family, expanding the clinical and mutational spectrum of CMD associated with CRPPA mutations. The proband had a homozygous deletion while the parents had a heterozygous deletion without symptoms.
WORLD JOURNAL OF CLINICAL CASES
(2021)
Article
Medicine, Research & Experimental
Hiroaki Ohara, Motoyasu Hosokawa, Tomonari Awaya, Atsuko Hagiwara, Ryo Kurosawa, Yukiya Sako, Megumu Ogawa, Masashi Ogasawara, Satoru Noguchi, Yuichi Goto, Ryosuke Takahashi, Ichizo Nishino, Masatoshi Hagiwara
Summary: The FKTN c.647+2084G>T variant causes Fukuyama congenital muscular dystrophy (FCMD) by creating a pseudo-exon. Researchers discovered that the branchpoint, essential for splicing reactions, can be a potential therapeutic target. Through the design of branchpoint-targeted antisense oligonucleotides (BP-AONs), they successfully restored normal FKTN mRNA and protein production in FCMD patient myotubes. This suggests that branchpoints could be potential targets in exon-skipping therapeutic strategies for genetic disorders.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Biochemistry & Molecular Biology
Luana Toniolo, Giuseppe Sirago, Nicola Fiotti, Emiliana Giacomello
Summary: A growing number of disorders are caused by mutations in the vesicular transport machinery, specifically in the Golgi Complex (GC). The GC is crucial for the organization and function of the early secretory pathway, and alterations in its form and function contribute to several disorders, including muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Motoi Kanagawa
Summary: Dystroglycanopathy is a group of muscular dystrophies caused by abnormal glycosylation of dystroglycan, with diverse clinical symptoms ranging from congenital to adult-onset types. Research in the 2010s has identified the sugar chain structure and functions of causative gene products, created various model mice for studying pathological mechanisms, and proposed treatment strategies based on glycosylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Domagoj Cikes, Kareem Elsayad, Erdinc Sezgin, Erika Koitai, Torma Ferenc, Michael Orthofer, Rebecca Yarwood, Leonhard X. Heinz, Vitaly Sedlyarov, Nasser Darwish Miranda, Adrian Taylor, Sophie Grapentine, Fathiya al-Murshedi, Anne Abot, Adelheid Weidinger, Candice Kutchukian, Colline Sanchez, Shane J. F. Cronin, Maria Novatchkova, Anoop Kavirayani, Thomas Schuetz, Bernhard Haubner, Lisa Haas, Astrid Hagelkruys, Suzanne Jackowski, Andrey Kozlov, Vincent Jacquemond, Claude Knauf, Giulio Superti-Furga, Eric Rullman, Thomas Gustafsson, John McDermot, Martin Lowe, Zsolt Radak, Jeffrey S. Chamberlain, Marica Bakovic, Siddharth Banka, Josef M. Penninger
Summary: Muscle degeneration is a common cause of frailty and dependency in inherited diseases and ageing. The enzyme PCYT2/ECT plays a critical role in muscle health. Deficiency in PCYT2 leads to severe disease and muscle weakness. Mechanistically, PCYT2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure. PCYT2 activity declines in ageing muscles and therapeutic delivery of PCYT2 improves muscle weakness.
Article
Clinical Neurology
Young Jun Ko, Anna Cho, Woo Joong Kim, Soo Yeon Kim, Byung Chan Lim, Hunmin Kim, Hee Hwang, Ji Eun Choi, Ki Joong Kim, Jong-Hee Chae
Summary: This study investigates the clinical and genetic characteristics of alpha-DG-related muscular dystrophy in the Korean pediatric population. The results show that alpha-DG-related muscular dystrophy has a wide range of genotypes and phenotypes according to ethnicity, suggesting the importance of stratified genetic testing for diagnosis.
NEUROMUSCULAR DISORDERS
(2023)
Article
Cardiac & Cardiovascular Systems
Enrico Bugiardini, Andreia M. Nunes, Ariany Oliveira-Santos, Marisela Dagda, Tatiana M. Fontelonga, Pamela Barraza-Flores, Alan M. Pittman, Jasper M. Morrow, Matthew Parton, Henry Houlden, Perry M. Elliott, Petros Syrris, Roderick P. Maas, Mohammed M. Akhtar, Benno Kusters, Joost Raaphorst, Meyke Schouten, Erik-Jan Kamsteeg, Baziel van Engelen, Michael G. Hanna, Rahul Phadke, Luis R. Lopes, Emma Matthews, Dean J. Burkin
Summary: This study describes the pathological changes caused by ITGA7 mutations in skeletal and cardiac muscle. Patients exhibited cardiac dysfunction and respiratory insufficiency, and mouse experiments also showed abnormalities related to the heart and muscles. The results suggest a critical role for integrin alpha 7 beta 1 in cardiac function.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Multidisciplinary Sciences
Paul T. Martin, Deborah A. Zygmunt, Anna Ashbrook, Sonia Hamilton, Davin Packer, Sharla M. Birch, Amanda K. Bettis, Cynthia J. Balog-Alvarez, Lee-Jae Guo, Peter P. Nghiem, Joe N. Kornegay
Summary: Short-term intravenous treatment of GRMD dogs with rAAVrh74.MHCK7.GALGT2 at high doses can induce muscle glycosylation and utrophin expression over a short 3-month interval, showing modest effects on muscle pathology and no significant improvement on muscle strength. Serum chemistry, hematology, and cardiac function measures were largely unchanged by treatment.
Article
Cell Biology
Brian J. Paleo, Kevin E. McElhanon, Hannah R. Bulgart, Kassidy K. Banford, Eric X. Beck, Kristina M. Sattler, Briana N. Goines, Shelby L. Ratcliff, Kelly E. Crowe, Noah Weisleder
Summary: TRIM72/MG53-mediated membrane repair can partially compensate for sarcolemmal fragility in DMD and the loss of membrane repair leads to increased pathology.
Article
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Prashant Monian, Chikdu Shivalila, Genliang Lu, Mamoru Shimizu, David Boulay, Karley Bussow, Michael Byrne, Adam Bezigian, Arindom Chatterjee, David Chew, Jigar Desai, Frank Favaloro, Jack Godfrey, Andrew Hoss, Naoki Iwamoto, Tomomi Kawamoto, Jayakanthan Kumarasamy, Anthony Lamattina, Amber Lindsey, Fangjun Liu, Richard Looby, Subramanian Marappan, Jake Metterville, Ronelle Murphy, Jeff Rossi, Tom Pu, Bijay Bhattarai, Stephany Standley, Snehlata Tripathi, Hailin Yang, Yuan Yin, Hui Yu, Cong Zhou, Luciano H. Apponi, Pachamuthu Kandasamy, Chandra Vargeese
Summary: The study describes chemically modified oligonucleotides called AIMers that can efficiently and specifically direct RNA-editing enzymes to edit endogenous transcripts. Fully chemically modified AIMers with chimeric backbones showed enhanced potency and editing efficiency compared to uniformly modified AIMers in vitro. In vivo, AIMers targeted to hepatocytes achieved significant editing without off-target effects in non-human primate liver. This study demonstrates the potential of AIMers for therapeutic applications.
NATURE BIOTECHNOLOGY
(2022)
Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Biochemistry & Molecular Biology
Justin Cohen, Alec DeSimone, Monkol Lek, Angela Lek
Summary: Facioscapulohumeral muscular dystrophy (FSHD) is a common type of muscular dystrophy, with limited therapeutic development due to complex genetics and poor mechanistic understanding; however, targeting DUX4 has shown promise in advancing clinical trials towards molecular therapies. The field is now poised to accelerate therapeutic discovery and testing with combined advances in FSHD research.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Genetics & Heredity
Sara Nagy, Tracy Lau, Shahryar Alavi, Ehsan Ghayoor Karimiani, Jalal Vallian, Bobby G. Ng, Samaneh Noroozi Asl, Javad Akhondian, Amir Bahreini, Omid Yaghini, Prech Uapinyoying, Carsten Bonnemann, Hudson H. Freeze, Vajira H. W. Dissanayake, Nirmala D. Sirisena, Miriam Schmidts, Henry Houlden, Andres Moreno-De-Luca, Reza Maroofian
Summary: Pathogenic variants in DPM genes cause congenital disorders of glycosylation, with DPM1 and DPM2 associated with muscle-eye-brain disease and DPM3 with isolated muscle disease-dystroglycanopathy. This study identified a rare homozygous DPM3 variant in five affected individuals, linking it to global developmental delay, intellectual disability, microcephaly, seizures, muscle weakness, and cardiomyopathy.
Article
Peripheral Vascular Disease
Hui-Yu Bai, Li-Juan Min, Bao-Shuai Shan, Jun Iwanami, Harumi Kan-no, Motoi Kanagawa, Masaki Mogi, Masatsugu Horiuchi
Summary: Ang II and A beta synergistically promote brain vascular smooth muscle cell senescence, possibly through enhancement of the p-ERK-p16-pRb signaling pathway, oxidative stress, and NF-kappa B/I kappa B activity.
AMERICAN JOURNAL OF HYPERTENSION
(2021)
Article
Biochemistry & Molecular Biology
Yingxue Wang, Parul Sharma, Matthew Jefferson, Weijiao Zhang, Ben Bone, Anja Kipar, David Bitto, Janine L. Coombes, Timothy Pearson, Angela Man, Alex Zhekova, Yongping Bao, Ralph A. Tripp, Simon R. Carding, Yohei Yamauchi, Ulrike Mayer, Penny P. Powell, James P. Stewart, Thomas Wileman
Summary: The study demonstrates that non-canonical autophagy in airway epithelial cells is a novel innate defense mechanism that restricts influenza virus infection and reduces lethal inflammation.
Article
Rheumatology
Hideki Nakamoto, Yuki Katanosaka, Ryota Chijimatsu, Daisuke Mori, Fengjun Xuan, Fumiko Yano, Yasunori Omata, Yuji Maenohara, Yasutaka Murahashi, Kohei Kawaguchi, Ryota Yamagami, Hiroshi Inui, Shuji Taketomi, Yuki Taniguchi, Motoi Kanagawa, Keiji Naruse, Sakae Tanaka, Taku Saito
Summary: This study reveals the regulation of articular cartilage by TRPV2 through Prg4 induction and suppression of ectopic ossification.
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Clinical Neurology
Chiseko Ikenaga, Hidetoshi Date, Motoi Kanagawa, Jun Mitsui, Hiroyuki Ishiura, Jun Yoshimura, Iago Pinal-Fernandez, Andrew L. Mammen, Thomas E. Lloyd, Shoji Tsuji, Jun Shimizu, Tatsushi Toda, Jun Goto
Summary: This study explored the molecular features of inclusion body myositis (IBM) and found that the differentially expressed genes and pathways in IBM and polymyositis were mostly comparable. However, the pathways related to cell adhesion molecules were upregulated in IBM. The study also discovered the overexpression of the epidermal cell junction protein cadherin 1 in the muscles of IBM, which could provide valuable insights into the pathological mechanisms of IBM.
ANNALS OF NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah J. Smith, Lacramioara Fabian, Adeel Sheikh, Ramil Noche, Xiucheng Cui, Steven A. Moore, James J. Dowling
Summary: Congenital muscular dystrophy type 1A (MDC1A) is a common genetic disorder caused by mutations in the LAMA2 gene. In this study, researchers used a zebrafish model to investigate the role of lysosome distribution in MDC1A. They found that abnormal lysosome distribution was associated with fiber detachment and could be improved by overexpression of a transcription factor called transcription factor EB. This suggests that targeting lysosome function may be a potential therapeutic strategy for treating MDC1A.
HUMAN MOLECULAR GENETICS
(2022)
Article
Genetics & Heredity
Megan A. Waldrop, Steven A. Moore, Katherine D. Mathews, Benjamin W. Darbro, Livja Medne, Richard Finkel, Anne M. Connolly, Thomas O. Crawford, Daniel Drachman, Nicolas Wein, Ali A. Habib, Monika A. Krzesniak-Swinarska, Craig M. Zaidman, James J. Collins, Manu Jokela, Bjarne Udd, John W. Day, Gloria Ortiz-Guerrero, Jeff Statland, Russell J. Butterfield, Diane M. Dunn, Robert B. Weiss, Kevin M. Flanigan
Summary: Deep intronic DMD mutations can be identified through muscle RNA analysis, which is an important diagnostic step for patients with abnormal dystrophin expression but negative genomic testing results. This study identified three types of pathogenic pseudoexon mutations and proposed potential treatment approaches based on the mutation type.
Article
Clinical Neurology
Payam Mohassel, Ning Chang, Kaoru Inoue, Angela Delaney, Ying Hu, Sandra Donkervoort, Dimah Saade, B. Jeanne Billioux, Brooke Meader, Rita Volochayev, Chamindra G. Konersman, Angela M. Kaindl, Chie-Hee Cho, Bianca Russell, Adrian Rodriguez, K. Wade Foster, A. Reghan Foley, Steven A. Moore, Peter L. Jones, Carsten G. Bonnemann, Takako Jones, Natalie D. Shaw
Summary: In this study, we identified individuals with arhinia who met the genetic and epigenetic criteria for FSHD2 and showed molecular hallmark of FSHD-DUX4 derepression and expression in vitro, but did not have the typical clinical phenotype of FSHD2. This suggests the presence of novel disease-modifying factors that operate as a switch between FSHD2 and arhinia phenotypes.
Article
Neurosciences
Nicole Becker, Steven A. Moore, Karra A. Jones
Summary: The inflammatory histopathology of dysferlinopathy is more similar to limb-girdle pattern muscular dystrophies than true inflammatory myopathies. Dysferlinopathy muscle biopsies have minimal inflammatory cell infiltrates, absent to focal MHC class I expression, and diffuse myofiber complement C5b-9 deposition.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Hideki Tokuoka, Rieko Imae, Hitomi Nakashima, Hiroshi Manya, Chiaki Masuda, Shunsuke Hoshino, Kazuhiro Kobayashi, Dirk J. Lefeber, Riki Matsumoto, Takashi Okada, Tamao Endo, Motoi Kanagawa, Tatsushi Toda
Summary: Ribitol-phosphate modifications are important for the maturation of alpha-dystroglycan, and defects in these modifications can lead to various diseases. This study demonstrates that prodrug treatments, specifically tetraacetylated CDP-ribitol, can ameliorate muscular dystrophy caused by defects in ISPD. These findings provide potential therapeutic options for muscular dystrophy and other glycosylation defects.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Anabel S. De La Garza-Rodea, Steven A. Moore, Jesus Zamora-Pineda, Eric P. Hoffman, Karishma Mistry, Ashok Kumar, Jonathan B. Strober, Piming Zhao, Jung H. Suh, Julie D. Saba
Summary: This study reveals that Duchenne muscular dystrophy (DMD) patients have increased expression of SPL and dysregulated S1P metabolism in skeletal muscles. Treatment with the SPL inhibitor LX2931 increases the number of muscle stem cells (SC), reduces leukocyte infiltration, and attenuates muscle inflammation and degeneration. The treatment also leads to changes in gene expression related to immune function, plasma membrane interactions, and axon guidance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Multidisciplinary Sciences
Yingxue Wang, Maria Ramos, Matthew Jefferson, Weijiao Zhang, Naiara Beraza, Simon Carding, Penny P. Powell, James P. Stewart, Ulrike Mayer, Thomas Wileman
Summary: The delivery of pathogens to lysosomes for degradation is an important defense mechanism against infection. The activation of the V-ATPase-ATG16L1 axis and the stabilization of NADPH oxidase play crucial roles in facilitating the conjugation of LC3 to pathogens and promoting their degradation. However, many microbes have developed strategies to inhibit LC3 recruitment and avoid lysosomal degradation by blocking ROS production and the V-ATPase-ATG16L1 axis.
Article
Pharmacology & Pharmacy
Catherine I. Soderstrom, Jennifer Larsen, Carolina Owen, David Gifondorwa, David Beidler, Florence H. Yong, Patricia Conrad, Hendrik Neubert, Steven A. Moore, Mohamed Hassanein
Summary: Duchenne muscular dystrophy (DMD) is a degenerative muscular disease with no cure. New advances in gene therapy and understanding of the disease have opened up new treatment opportunities. This article describes a novel Western blot method for monitoring dystrophin expression and assessing treatment efficacy.
Article
Medicine, General & Internal
Arnold H. H. Menezes, Yutaka Sato, Brian J. J. Dlouhy, Karra A. A. Jones, Steven A. A. Moore
Summary: A Caucasian female neonate with ventriculus terminalis cyst, extra-axial conofilar cyst, and tethered lipomatous filum underwent surgical intervention due to progressive cyst enlargement. The cyst was excised and the lipomatous filum was sectioned during the surgery. The child had a good recovery without deficits at 4-year follow up.
JOURNAL OF MEDICAL CASE REPORTS
(2023)
Article
Multidisciplinary Sciences
Kaoru Inoue, Hamed Bostan, MaKenna R. Browne, Owen F. Bevis, Carl D. Bortner, Steven A. Moore, Aaron A. Stence, Negin P. Martin, Shih-Heng Chen, Adam B. Burkholder, Jian-Liang Li, Natalie D. Shaw
Summary: SMCHD1 mutations cause congenital arhinia and FSHD2. Loss of SMCHD1 activity leads to DUX4 expression and cell death in placode cells derived from hESCs and iPSCs. Herpesvirus infection may amplify DUX4 expression in SMCHD1 KO cells, indicating an environmental disease modifier.
Article
Cell Biology
Agathe Marcelot, Felipe Rodriguez-Tirado, Philippe Cuniasse, Mei-ling Joiner, Simona Miron, Alexey A. Soshnev, Mimi Fang, Miles A. Pufall, Katherine D. Mathews, Steven A. Moore, Sophie Zinn-Justin, Pamela K. Geyer
Summary: Barrier-to-autointegration factor (BAF) is an essential component of the nuclear lamina that regulates gene expression, cell cycle progression, and nuclear integrity. A dominant pathogenic BAF variant, Gly16Arg, has been identified in a patient with progressive neuromuscular weakness, causing changes in chromatin structure and nuclear functions. This study demonstrates how a missense mutation can alter protein conformation and lead to a dominant disease phenotype.