Article
Medicine, General & Internal
Taylor Gould, Takako Jones, Peter L. Jones
Summary: The true prevalence of facioscapulohumeral muscular dystrophy (FSHD) remains unknown, but epigenetic analysis could provide a diagnostic pathway for sequence-based diagnosis. Conflicting results from studies assessing DNA methylation at the FSHD locus have made the utility of this technique controversial for FSHD diagnosis.
Article
Biochemistry & Molecular Biology
Camille Laberthonniere, Megane Delourme, Raphael Chevalier, Camille Dion, Benjamin Ganne, David Hirst, Leslie Caron, Pierre Perrin, Jose Adelaide, Max Chaffanet, Shifeng Xue, Karine Nguyen, Bruno Reversade, Jerome Dejardin, Anais Baudot, Jerome D. Robin, Frederique Magdinier
Summary: Mutations in the SMCHD1 gene are associated with various genetic syndromes. This study investigated the impact of SMCHD1 variants on chromatin organization and gene regulation in two rare genetic diseases. The findings suggest that SMCHD1 is involved in chromatin compaction, insulation, and gene regulation, both directly and indirectly through master transcription factors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ngoc Lu-Nguyen, Alberto Malerba, Shan Herath, George Dickson, Linda Popplewell
Summary: Aberrant expression of the DUX4 gene in skeletal muscle causes muscle deterioration in FSHD. Disrupting the polyadenylation signal can prevent its expression. Using antisense approaches to reduce DUX4 expression has shown promising results in improving muscle pathology and strength.
HUMAN MOLECULAR GENETICS
(2021)
Article
Genetics & Heredity
Claudia Strafella, Valerio Caputo, Sara Bortolani, Eleonora Torchia, Domenica Megalizzi, Giulia Trastulli, Mauro Monforte, Luca Colantoni, Carlo Caltagirone, Enzo Ricci, Giorgio Tasca, Raffaella Cascella, Emiliano Giardina
Summary: This study used Whole Exome Sequencing to investigate the genetic contributors to Facioscapulohumeral Dystrophy (FSHD) and their potential impact on disease severity. The analysis identified several known and candidate genes that may contribute to disease heterogeneity and expressivity. Additionally, the study emphasized the importance of extending the analysis to family members to better understand single cases and improve genotype-phenotype correlations in FSHD-affected families.
FRONTIERS IN GENETICS
(2023)
Article
Chemistry, Analytical
Lahari Uppuluri, Tanaya Jadhav, Yilin Wang, Ming Xiao
Summary: This study introduces a universal multicolor mapping strategy in nanochannels combining conventional sequence motif labeling with Cas9-mediated target-specific labeling, which enables accurate detection of structural variations and estimation of genomic repeat copy numbers. The method was validated for assessing biomarkers related to muscular dystrophy and aging-related diseases.
ANALYTICAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Anna Karpukhina, Eugenia Tiukacheva, Carla Dib, Yegor S. Vassetzky
Summary: This review discusses the regulation of DUX4 gene expression, including various genetic and epigenetic mechanisms, and its roles in both normal and diseased states, providing insights for future research and clinical therapies.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Fraser Philp, Richa Kulshrestha, Nicholas Emery, Marco Arkesteijn, Anand Pandyan, Tracey Willis
Summary: This study aimed to evaluate the effect of a single intermittent arm cycling exercise on people affected by FSHD. The results showed that intermittent arm cycling was feasible for FSHD patients and could improve shoulder function and strength.
Article
Biochemistry & Molecular Biology
Victor Corasolla Carregari, Mauro Monforte, Giuseppe Di Maio, Luisa Pieroni, Andrea Urbani, Enzo Ricci, Giorgio Tasca
Summary: The study used proteomic analysis to identify specific protein expression patterns in interstitial fluids and serum samples from FSHD patients at different disease stages, revealing inflammatory responses and muscle regeneration defects during the active phase. Additionally, potential biomarkers were discovered.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Christopher R. S. Banerji, Peter S. Zammit
Summary: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by skeletal muscle weakness and wasting due to epigenetic derepression of the D4Z4 macrosatellite, leading to transcription of DUX4 which activates target genes. PAX7 suppression serves as a reliable biomarker for FSHD, but its link to genomic changes and DUX4 remains unclear. Understanding the roles of DUX4 and PAX7 in FSHD pathology can deepen knowledge of the disease through interactions with the immune system and muscle regeneration.
EMBO MOLECULAR MEDICINE
(2021)
Review
Clinical Neurology
Valentina Salsi, Gaetano Nicola Alfio Vattemi, Rossella Ginevra Tupler
Summary: We analysed 121 literature reports published between 2021 and 2023 to assess the most recent advances in FSHD clinical and molecular research.
CURRENT OPINION IN NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Sujatha Jagannathan
Summary: This minireview summarizes the current state of research in DUX4 and FSHD biology, highlighting key areas for further investigation to better understand DUX4 regulation and FSHD pathogenesis. The review also emphasizes post-transcriptional regulation of DUX4 through changes in RNA and protein stability, which may underlie key features of FSHD pathophysiology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Review
Genetics & Heredity
Salvatore Martino, Pietro Salvatore Carollo, Viviana Barra
Summary: During embryonic development, stem cells differentiate and specialize for different functions within the organism. This process relies on complex gene transcription programs, epigenetic modifications, and the architecture of chromatin in the nucleus. The regulation of three-dimensional chromatin structure and the role of the nuclear lamina in neurogenesis are discussed in this mini review.
Article
Biochemistry & Molecular Biology
Darko Bosnakovski, David Oyler, Ana Mitanoska, Madison Douglas, Elizabeth T. Ener, Ahmed S. Shams, Michael Kyba
Summary: FSHD is a disease caused by loss of silencing of the DUX4 gene, but the presence of the DUX4 protein in affected muscle has not been directly detected. This study used an animal model to investigate the extent of muscle regeneration following DUX4-mediated degeneration. The results showed that muscle histology could recover significantly after DUX4 expression was switched off, but the fibroadipogenic progenitor compartment remained elevated and the recovered muscle had a propensity for severe fibrosis. These findings have potential implications for therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Rehabilitation
Elena Carraro, Lucia Catherine Greco, Andrea Lizio, Maria Beretta, Susanna Pozzi, Jacopo Casiraghi, Stefano Becchiati, Fatmira Beshiri, Maria Chiara Frisoni, Felicia Iossa, Chad Heatwole, Valeria Sansone
Summary: The purpose of this study was to validate and test the Italian translation of the Facioscapulohumeral Muscular Dystrophy - Health Index (FSHD-HI) in an Italian population affected by FSHD. The translated instrument was found to be relevant, reliable, and significantly associated with motor function, respiratory function, and perceived quality of life assessments. Overall, the Italian FSHD-HI is a valid and well-suited measurement of disease burden in FSHD patients.
DISABILITY AND REHABILITATION
(2023)
Article
Biochemical Research Methods
Sarah M. Mangiameli, Haiqi Chen, Andrew S. Earl, Julie A. Dobkin, Daniel Lesman, Jason D. Buenrostro, Fei Chen
Summary: Photoselective sequencing is a new method for genomic and epigenomic profiling in morphologically distinct regions. It uses targeted illumination to selectively unblock a photocaged fragment library, enabling sequencing-based readout in microscopically identified spatial regions. The method was validated by analyzing chromatin accessibility profiles of fluorescently-labeled cell types in the mouse brain and comparing with published data. Photoselective sequencing is a flexible and generalizable platform for studying the interplay of spatial structures with genomic and epigenomic properties.
Article
Genetics & Heredity
Richard J. L. F. Lemmers, Patrick J. van der Vliet, Ana Blatnik, Judit Balog, Janez Zidar, Don Henderson, Rianne Goselink, Stephen J. Tapscott, Nicol C. Voermans, Rabi Tawil, George W. A. M. Padberg, Baziel G. M. van Engelen, Silvere M. van der Maarel
Summary: This study identified two FSHD families in which the disease is caused by a de novo D4Z4 repeat exchange between chromosomes 4 and 10, leading to repeat contraction and DUX4 expression from chromosome 10. The genetic lesion causal to FSHD in these families is physically separated from other candidate genes on chromosome 4. Muscle cell cultures from affected family members exhibited the characteristic molecular features of FSHD, indicating that DUX4 derepression is the dominant disease pathway for FSHD.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Chao-Jen Wong, Leo Wang, V. Michael Holers, Ashley Frazer-Abel, Silvere M. van der Maarel, Rabi Tawil, Jeffrey M. Statland, Stephen J. Tapscott
Summary: Advances in understanding the pathophysiology of facioscapulohumeral dystrophy (FSHD) have led to the development of therapeutic approaches and the need for biomarkers of disease activity and progression. This study found elevated complement components in plasma from FSHD patients, suggesting the potential use of complement activation measurements as a non-invasive assessment of FSHD disease activity, progression, and response to therapies.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Richard J. L. F. Lemmers, Patrick J. van der Vliet, David San Leon Granado, Nienke van der Stoep, Henk Buermans, Robin van Schendel, Joost Schimmel, Marianne de Visser, Rudy van Coster, Marc Jeanpierre, Pascal Laforet, Meena Upadhyaya, Baziel van Engelen, Sabrina Sacconi, Rabi Tawil, Nicol C. Voermans, Mark Rogers, Silvere M. van der Maarel
Summary: Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disease that can be diagnosed by analyzing the D4Z4 repeat on chromosome 4, but atypical rearrangement may affect the accuracy of diagnosis. Research shows that some DPED alleles are derived from an ancient founder allele, and the deletion of genetic elements in some DPED alleles may require reassessment of their role in the pathogenesis of the disease.
HUMAN MOLECULAR GENETICS
(2022)
Editorial Material
Clinical Neurology
L. R. van den Bersselaar, S. Riazi, M. M. J. Snoeck, H. Jungbluth, N. C. Voermans
NEUROMUSCULAR DISORDERS
(2022)
Article
Multidisciplinary Sciences
Anita van den Heuvel, Saskia Lassche, Karlien Mul, Anna Greco, David San Leon Granado, Arend Heerschap, Benno Kusters, Stephen J. Tapscott, Nicol C. Voermans, Baziel G. M. van Engelen, Silvere M. van der Maarel
Summary: This study investigates FSHD-associated transcriptome signatures in FSHD skeletal muscle biopsies and explores their correlation with various disease-associated factors. It also analyzes the predictive power of imaging-based biomarkers for detecting FSHD signatures in clinical trials. Additionally, the study examines the role of infiltrating non-muscle cell types in FSHD signature expression.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Sujatha Jagannathan, Jessica C. de Greef, Lawrence J. Hayward, Kyoko Yokomori, Davide Gabellini, Karlien Mul, Sabrina Sacconi, Jamshid Arjomand, June Kinoshita, Scott Q. Harper
Summary: Facioscapulohumeral muscular dystrophy (FSHD) is a common genetic myopathy characterized by progressive muscle wasting. The recent FSHD International Research Congress provided a platform for researchers and clinicians to share the latest advances in understanding the disease mechanisms and discuss therapeutic strategies and clinical outcome measures.
Article
Clinical Neurology
Christine C. Bruels, Hannah R. Littel, Audrey L. Daugherty, Seth Stafki, Elicia A. Estrella, Emily S. McGaughy, Don Truong, Jonathan P. Badalamenti, Lynn Pais, Vijay S. Ganesh, Anne O'Donnell-Luria, Heather J. Stalker, Yang Wang, Christin Collins, Andrea Behlmann, Richard J. L. F. Lemmers, Silvere M. van der Maarel, Regina Laine, Partha S. Ghosh, Basil T. Darras, Carla D. Zingariello, Christina A. Pacak, Louis M. Kunkel, Peter B. Kang
Summary: Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical testing. This study found that nanopore genomic long-read sequencing can help identify previously undetected pathogenic variants, streamlining genetic diagnostic approaches for muscular dystrophy.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Review
Clinical Neurology
Mara S. S. Tihaya, Karlien Mul, Judit Balog, Jessica C. C. de Greef, Stephen J. J. Tapscott, Rabi Tawil, Jeffrey M. M. Statland, Silvere M. van der Maarel
Summary: Advances in the molecular understanding of FSHD have revealed the epigenetic de-repression of the DUX4 gene in skeletal muscle as the cause of the disease. This has led to the identification of potential targeted therapies and improved understanding of the disease mechanism. The development of disease modifying treatments, ongoing clinical trials, and specific outcome measures and assessment tools for FSHD are discussed in this review.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Cell Biology
Cyriel Sebastiaan Olie, Adan Pinto-Fernandez, Andreas Damianou, Iolanda Vendrell, Hailiang Mei, Bianca den Hamer, Erik van der Wal, Jessica C. de Greef, Vered Raz, Benedikt M. Kessler
Summary: The ubiquitin proteasomal system plays a critical role in muscle physiology, but the function of deubiquitinating enzymes (DUBs) in muscle cells remains poorly understood. Through a genetic screen, we discovered that the depletion of USP18, a DUB, affects muscle cell differentiation. USP18 regulates differentiation initiation and maintenance independently of ISG15 and the ISG response. Alterations in gene networks and protein expression profiles were observed in the absence of USP18, leading to disrupted calcium homeostasis and reduced contractile force.
CELL DEATH & DISEASE
(2023)
Article
Biology
Darina Sikrova, Alessandra M. Testa, Iris Willemsen, Anita van den Heuvel, Stephen J. Tapscott, Lucia Daxinger, Judit Balog, Silvere M. van der Maarel
Summary: Facioscapulohumeral muscular dystrophy (FSHD) is caused by the derepression of the 4q-linked D4Z4 macrosatellite repeat, leading to inappropriate expression of the D4Z4 repeat-encoded DUX4 gene in skeletal muscle. Germline mutations in chromatin modifiers SMCHD1 and LRIF1 can result in D4Z4 chromatin relaxation. Alternative modes of repression of D4Z4 by SMCHD1 and LRIF1 are identified, providing insights into the understanding of FSHD.
COMMUNICATIONS BIOLOGY
(2023)
Meeting Abstract
Clinical Neurology
Dana L. E. Vergoossen, Jaap J. Plomp, Christoph J. Gstottner, Yvonne E. Fillie-Grijpma, Roy Augustinus, Robyn L. K. Verpalen, Manfred Wuhrer, Paul W. H. I. Parren, Elena Dominguez-Vega, Silvere M. van der Maarel, Jan J. G. M. Verschuuren, Maartje G. Huijbers
Meeting Abstract
Clinical Neurology
Laurent M. Paardekooper, Yvonne E. Fillie-Grijpma, Alita J. van der Sluijs-Gelling, Mihaela Zlei, Remco van Doorn, Maarten H. Vermeer, Manuela Paunovic, Maarten J. Titulaer, Silvere M. van der Maarel, Jacques J. M. van Dongen, Jan J. Verschuuren, Maartje G. Huijbers
Meeting Abstract
Immunology
Laurent M. Paardekooper, Yvonne E. Fillie Grijpma, Alita J. Van der Sluijs Gelling, Mihaela Zlei, Remco Van Doorn, Maarten H. Vermeer, Silvere M. Van der Maarel, Jacques J. M. Van Dongen, Jan J. Verschuuren, Maartje G. Huijbers
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Meeting Abstract
Immunology
Dana L. Vergoossen, Jaap J. Plomp, Christoph Gstottner, Yvonne E. Fillie Grijpma, Roy Augustinus, Robyn Verpalen, Manfred Wuhrer, Paul W. Parren, Elena Dominguez Vega, Silvere M. Van der Maarel, Jan J. Verschuuren, Maartje G. Huijbers
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
C. F. M. Menck, R. S. Galhardo, A. Quinet
Summary: Studies have shown that xeroderma pigmentosum variant (XP-V) patients have mutations in the POLH gene, resulting in a high frequency of skin tumors. However, it is paradoxical that the translesion synthesis DNA polymerase eta (Pol η) in these patients can actually suppress mutations, and the mechanism behind this is still unclear. Recent evidence suggests that cyclobutane pyrimidine dimers (CPDs) play an instructional role for Pol η, enabling accurate replication of these lesions, and the mutagenic effects induced by UV radiation are caused by the deamination of C-containing CPDs. This process leads to C>T transitions, which are the most common mutations in skin cancers. The delayed replication in XP-V cells amplifies the deamination of C in CPDs and increases the burden of C>T mutations through the activity of backup TLS polymerases.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2024)
