Review
Cell Biology
Massimo Zeviani, Carlo Viscomi
Summary: Mitochondria are vital organelles responsible for generating energy in cells. Mutations in mtDNA or nuclear genes can lead to complex neurological disorders. Understanding these diseases is essential for the field of mitochondrial medicine due to the diverse genetic and phenotypic heterogeneity.
Article
Biochemistry & Molecular Biology
Biyi Chen, Nastaran Daneshgar, Hsiang-Chun Lee, Long-Sheng Song, Dao-Fu Dai
Summary: Mitochondrial oxidative stress plays a role in aging and various cardiovascular diseases. Its involvement in bradyarrhythmia is less understood. In a mouse model of Leigh Syndrome (LS), mitochondrial antioxidant treatment improved bradyarrhythmia and extended lifespan. Increased reactive oxygen species (ROS) in the LS heart were observed and abolished by mitochondrial antioxidant treatment. This study suggests the direct mechanistic roles of mitochondrial ROS in bradyarrhythmia and highlights the potential clinical application of mitochondrial-targeted antioxidants in LS patients.
Article
Genetics & Heredity
Marta Zawadzka, Magdalena Krygier, Malgorzata Pawlowicz, Matheus Vernet Machado Bressan Wilke, Karolina Rutkowska, Naig Gueguen, Valerie Desquiret-Dumas, Eric W. Klee, Lisa A. Schimmenti, Jaroslaw Slawek, Vincent Procaccio, Rafal Ploski, Maria Mazurkiewicz-Beldzinska
Summary: Leigh syndrome is a progressive neurodegenerative disease with extensive clinical and biochemical features. This study describes three Polish patients and provides further evidence for the association of DNAJC30 gene variants with Leigh syndrome. DNAJC30-associated Leigh syndrome exhibits clinical heterogeneity with variable age at onset, movement disorder phenotype, and blood lactate level.
Review
Biochemistry & Molecular Biology
Jane H. Frederiksen, Sara B. Jensen, Zeynep Tumer, Thomas V. O. Hansen
Summary: Lynch syndrome is a common hereditary cancer predisposition syndrome caused by pathogenic variants in DNA mismatch repair genes, emphasizing the importance of clear genetic diagnosis for clinical management. Functional assays can provide insights into difficult-to-predict variants. Future perspectives include high-throughput functional analyses of MMR genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Allison Hanaford, Simon C. Johnson
Summary: Genetic mitochondrial diseases pose a significant challenge to human health, and recent evidence suggests that the immune system plays a key role in the pathogenesis of at least some forms of these diseases.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biology
C. J. Kelly, Reid K. Couch, Vivian T. Ha, Camille M. Bodart, Judy Wu, Sydney Huff, Nicole T. Herrel, Hyunsung D. Kim, Azaad O. Zimmermann, Jessica Shattuck, Yu-Chen Pan, Matt Kaeberlein, Anthony S. Grillo
Summary: Mice lacking Complex I subunit NDUFS4 exhibit mitochondrial dysfunction and the abnormal iron homeostasis may contribute to the progression of Leigh Syndrome and other mitochondrial disorders.
Article
Genetics & Heredity
Anna Ardissone, Claudio Bruno, Daria Diodato, Alice Donati, Daniele Ghezzi, Eleonora Lamantea, Costanza Lamperti, Michelangelo Mancuso, Diego Martinelli, Guido Primiano, Elena Procopio, Anna Rubegni, Filippo Santorelli, Maria Cristina Schiaffino, Serenella Servidei, Flavia Tubili, Enrico Bertini, Isabella Moroni
Summary: Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with mitochondrial dysfunction. This study reviewed data from 122 genetically confirmed LS patients, finding that central nervous system involvement was predominant and often associated with complex I and IV deficiencies. SURF1 mutations were linked to poor prognosis in this large cohort.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Neurosciences
Hayley Christy Miller, Roan Louw, Michelle Mereis, Gerda Venter, John-Drew Boshoff, Liesel Mienie, Mari van Reenen, Marianne Venter, Jeremie Zander Lindeque, Adan Dominguez-Martinez, Albert Quintana, Francois Hendrikus van der Westhuizen
Summary: This study investigated the potential protective effect of metallothioneins (MTs) in a complex I-deficient mouse model, but found that overexpression of MT1 did not lead to improvements in survival, growth, locomotor activity, balance, or motor coordination. Despite subtle reductions in neuroinflammatory markers in certain brain regions, there were no significant differences in metabolomics profiles, gene expression, or ROS levels between the MT1-overexpressing mice and control mice. These findings suggest that MT1 does not protect against impaired motor activity or improve survival in this mitochondrial disease model, possibly due to the unexpected absence of increased oxidative stress and metabolic imbalance. However, tissue-specific observations and differential MT1 expression may indicate a potential tissue- or cell-specific role for MTs in these mice.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Inn-Chi Lee, Kuo-Liang Chiang
Summary: Mutations in the SURF1 gene can cause Leigh syndrome, characterized by severe symptoms and varying disease courses. Treatment options such as a ketogenic diet and coenzyme Q supplementation may provide some relief, but overall therapeutic efficacy remains limited.
Article
Anesthesiology
Kira A. Spencer, Michael Mulholland, John Snell, Miranda Howe, Katerina James, Allison R. Hanaford, Philip G. Morgan, Margaret Sedensky, Simon C. Johnson
Summary: The study found that isoflurane is toxic in the Ndufs4(-/-) model of Leigh syndrome. The toxic effects depend on the status of underlying neurologic disease, and can be prevented by the CSF1R inhibitor pexidartinib, and influenced by oxygen concentration in the carrier gas.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Article
Genetics & Heredity
Can Ozlu, Priya Chelliah, Hamza Dahshi, Daniel Horton, Veronica B. Edgar, Souad Messahel, Saima Kayani
Summary: This study aims to further describe the ECHS1 deficiency phenotype using medical history questionnaires and standardized tools. Findings illustrate a severely disabling condition causing severe developmental delays, regression, dystonia/hypotonia and movement disorders, commonly with symptom onset in infancy, classical MRI findings involving the basal ganglia, and variability in biochemical profile.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Oncology
Jin-Young Yoon, Nastaran Daneshgar, Yi Chu, Biyi Chen, Marco Hefti, Ajit Vikram, Kaikobad Irani, Long-Sheng Song, Charles Brenner, E. Dale Abel, Barry London, Dao-Fu Dai
Summary: This study reveals the mechanistic explanations for cardiac bradyarrhythmia, diastolic dysfunction, and neuronal apoptosis observed in models of Leigh syndrome (LS).
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Clinical Neurology
Sarah L. Stenton, Marketa Tesarova, Natalia L. Sheremet, Claudia Catarino, Valerio Carelli, Elzbieta Ciara, Kathryn Curry, Martin Engvall, Leah R. Fleming, Peter Freisinger, Katarzyna Iwanicka-Pronicka, Elzbieta Jurkiewicz, Thomas Klopstock, Mary K. Koenig, Hana Kolarova, Bohdan Kousal, Tatiana Krylova, Chiara La Morgia, Lenka Noskova, Dorota Piekutowska-Abramczuk, Sam N. Russo, Viktor Stranecky, Iveta Tothova, Frank Traisk, Holger Prokisch
Summary: The study identified 28 previously unreported individuals carrying the DNAJC30 variant, expanding the spectrum of Leber hereditary optic neuropathy and Leigh syndrome. The findings confirmed sex-dependent incomplete penetrance of the homozygous variant and the association of DNAJC30 with Leigh syndrome.
Article
Cell Biology
Michela Murdocca, Paola Spitalieri, Claudia De Masi, Ion Udroiu, Jessica Marinaccio, Massimo Sanchez, Rosa Valentina Talarico, Chiara Fiorillo, Monica D'Adamo, Paolo Sbraccia, Maria Rosaria D'Apice, Giuseppe Novelli, Antonella Sgura, Federica Sangiuolo
Summary: MDPL Syndrome is a rare systemic disorder often caused by a variant in the POLD1 gene, resulting in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy. Cellular phenotype analysis of MDPL fibroblasts revealed nuclear envelope anomalies, accumulation of prelamin A, and presence of micronuclei, as well as cellular senescence and delayed recovery from DNA induced-damage. Additionally, telomere dysfunction was found to be a key feature in MDPL, suggesting an alteration in DNA replication/repair function of POLD1 as the primary pathogenetic cause.
Article
Clinical Neurology
Jingwei Lyu, Yuying Zhao, Na Zhang, Xuebi Xu, Rui Zheng, Wenfei Yu, Wang Xin, Chuanzhu Yan, Kunqian Ji
Summary: Leigh syndrome (LS) is a common mitochondrial encephalopathy disease in infants, and effective therapy is still lacking. A study found that the pan-peroxisome proliferator-activated receptor agonist Bezafibrate (BEZ) has therapeutic effects on a LS animal model, Ndufs4 knockout (KO) mice, improving survival and attenuating disease progression. The study also showed decreased oxidative stress and stunted growth. However, the therapeutic effects of BEZ were not related to mitochondrial biogenesis or enhanced metabolism, but rather to the activation of energy-saving metabolism in mice. The exact mechanism of action still requires further study.
Article
Rheumatology
Jean-Baptiste Vulsteke, Rita Derua, Sylvain Dubucquoi, Frederic Coutant, Sebastien Sanges, David Goncalves, Greet Wuyts, Petra De Haes, Daniel Blockmans, Wim A. Wuyts, Kristl G. Claeys, Ellen De Langhe, Nicole Fabien, Xavier Bossuyt
Summary: New and known antisynthetase autoantibodies (ASAs) were discovered and detected through protein immunoprecipitation combined with gel-free liquid chromatography-tandem mass spectrometry (IP-MS). The dominant cognate ARS autoantigen of the newly discovered anti-Ly ASA specificity was identified. Unbiased and targeted IP-MS are promising methods for discovery and detection of autoantibodies.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Beata Mrozikiewicz-Rakowska, Ilona Szablowska-Gadomska, Dominik Cysewski, Stefan Rudzinski, Rafal Ploski, Piotr Gasperowicz, Magdalena Konarzewska, Jakub Zielinski, Mateusz Mieczkowski, Damian Sienko, Tomasz Grzela, Maria Noszczyk, Barbara Paleska, Leszek Czupryniak, Malgorzata Lewandowska-Szumiel
Summary: This study examined the safety and efficacy of allogenic adipose-derived stem cells (ADSCs) in diabetic foot ulcer treatment. The results showed that patients treated with ADSCs had faster wound healing and smaller wound size, which correlated with molecular changes. These findings have important implications for the development of cell-based therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Sarah Dewilde, Glenn Philips, Sandra Paci, Jon Beauchamp, Silvia Chiroli, Casey Quinn, Laura Day, Mark Larkin, Jacqueline Palace, Sonia Berrih-Aknin, Kristl G. Claeys, Srikanth Muppidi, Renato Mantegazza, Francesco Sacca, Andreas Meisel, Guillaume Bassez, Hiroyuki Murai, M. F. Janssen
Summary: This study aims to explore the impact of myasthenia gravis (MG) on health-related quality of life (HRQoL) from the perspective of patients. The results showed that MG significantly affects patients' daily activities, anxiety and depression, fatigue, breathing, and vision. The impact of the disease becomes more severe with increasing disease severity.
Article
Clinical Neurology
Alexander de Bruyn, Federica Montagnese, Sonja Holm-Yildiz, Nanna Scharff Poulsen, Tanya Stojkovic, Anthony Behin, Johanna Palmio, Manu Jokela, Jan L. De Bleecker, Marianne de Visser, Anneke J. van der Kooi, Leroy ten Dam, Cristina Dominguez Gonzalez, Lorenzo Maggi, Annamaria Gallone, Anna Kostera-Pruszczyk, Anna Macias, Anna Lusakowska, Velina Nedkova, Montse Olive, Rodrigo Alvarez-Velasco, Julia Wanschitz, Carmen Paradas, Fabiola Mavillard, Giorgia Querin, Gorka Fernandez-Eulate, Ros Quinlivan, Maggie C. Walter, Christophe E. Depuydt, Bjarne Udd, John Vissing, Benedikt Schoser, Kristl G. Claeys
Summary: This study examined the clinical and genetic spectrum of ANO5-related muscle diseases in a large European cohort, and searched for potential genotype-phenotype correlations. The results showed variable clinical phenotypes including limb-girdle muscular dystrophy type 12, distal muscular dystrophy type 3, pseudometabolic myopathy, and asymptomatic hyperCKaemia. Male patients had a higher prevalence in all subgroups, and there was no correlation between age, symptom onset, and motor outcomes. This study provides valuable information for clinical follow-up and the design of clinical trials.
Article
Clinical Neurology
Nicholas M. Allen, Mark O'Rahelly, Bruno Eymard, Mondher Chouchane, Andreas Hahn, Gerry Kearns, Dae-Seong Kim, Shin Yun Byun, Cam-Tu Emilie Nguyen, Ulrike Schara-Schmidt, Heike Koelbel, Adela Della Marina, Christiane Schneider-Gold, Kathryn Roefke, Andrea Thieme, Peter Van den Bergh, Gloria Avalos, Rodrigo Alvarez-Velasco, Daniel Natera-de Benito, Man Hin Mark Cheng, Wing Ki Chan, Hoi Shan Wan, Mary Ann Thomas, Lauren Borch, Julie Lauzon, Cornelia Kornblum, Jens Reimann, Andreas Mueller, Thierry Kuntzer, Fiona Norwood, Sithara Ramdas, Leslie W. Jacobson, Xiaobo Jie, Miguel A. Fernandez-Garcia, Elizabeth Wraige, Ming Lim, Jean Pierre Lin, Kristl G. Claeys, Selma Aktas, Maryam Oskoui, Yael Hacohen, Ameneh Masud, M. Isabel Leite, Jacqueline Palace, Darryl De Vivo, Angela Vincent, Heinz Jungbluth
Summary: Allen et al. found that exposure to maternal antibodies against fetal acetylcholine receptor (fAChR) during pregnancy can result in a wide range of persistent neuromuscular disorders in offspring. Immune-based therapies during pregnancy can prevent these disorders, while oral salbutamol is an effective treatment for the affected children.
Article
Clinical Neurology
Bram De Wel, Kristl G. Claeys
Summary: We appreciate Professor Kawada's comments on our article. The study involved three evaluations of all participants at strict 1-year intervals, without any missed visits or missing data. The researchers also ensured phenotypic homogeneity by excluding patients with isolated hyperCKemia and defining disease onset based on clinical symptoms of LGMDR12.
Article
Multidisciplinary Sciences
Katarzyna Jaskiewicz, Magdalena Maleszka-Kurpiel, Andrzej Michalski, Rafal Ploski, Malgorzata Rydzanicz, Marzena Gajecka
Summary: This study identified male sex, eye rubbing, time of using a computer after work, and dust in the working environment as substantial risk factors for keratoconus, which affect the corneal epithelium. Gene expression analysis showed that eye rubbing may cause cellular stress and affect the phenotype of keratoconus.
Article
Geriatrics & Gerontology
Bram De Wel, Lotte Huysmans, Christophe E. Depuydt, Veerle Goosens, Ronald Peeters, Filipa P. Santos, Dietmar R. Thal, Patrick Dupont, Frederik Maes, Kristl G. Claeys
Summary: The relationship between PDFF measurements with MRI and histopathological changes in muscle biopsies of patients with LGMDR12 is still unclear. The spatial distribution of fat replacement within the muscles affected by LGMDR12 is also unknown.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Genetics & Heredity
Justyna Paprocka, Aleksandra Jezela-Stanek, Robert Smigiel, Anna Walczak, Hanna Mierzewska, Anna Kutkowska-Kazmierczak, Rafal Ploski, Ewa Emich-Widera, Barbara Steinborn
Summary: This study analyzed the first Polish patients with confirmed heterozygous pathogenic and potentially pathogenic KIF1A variants. Three novel variants were identified. The authors highlighted the difficulties in classifying particular syndromes due to non-specific and overlapping signs and symptoms, sometimes observed only temporarily.
Article
Clinical Neurology
Lotte Huysmans, Bram De Wel, Kristl G. Claeys, Frederik Maes
Summary: Muscular dystrophies (MD) result in progressive muscle weakness, and fat-sensitive MRI can be used to assess disease progression by quantifying the fat fraction percentage (FF%) per muscle. Precise 3D muscle segmentation is necessary for accurate fat replacement quantification, but manual segmentation is time-consuming. To address this, the researchers used deep learning to train AI models to segment muscles in leg MRI images. The results showed high segmentation accuracy, regardless of fat infiltration levels and MRI field of view.
FRONTIERS IN NEUROLOGY
(2023)
Article
Genetics & Heredity
Katarzyna Bzdega, Mateusz Biela, Gail H. Deutsch, Joseph A. Kitzmiller, Malgorzata Rydzanicz, Rafal Ploski, Jeffrey A. Whitsett, Robert Smigiel, Justyna A. Karolak
Summary: Congenital alveolar dysplasia (CAD) is a rare and lethal lung developmental disorder characterized by respiratory failure and pulmonary arterial hypertension. Most CAD cases are associated with copy-number variant (CNV) deletions at 17q23.1q23.2 or 5p12. This study reports a novel non-recurrent CNV deletion involving TBX4 gene in a CAD patient, providing evidence that perturbations in TBX4, rather than TBX2, cause severe lung phenotypes in humans.
Article
Biochemistry & Molecular Biology
Anna Kloska, Agata Gielczyk, Tomasz Grzybowski, Rafal Ploski, Sylwester M. Kloska, Tomasz Marciniak, Krzysztof Palczynski, Urszula Rogalla-Ladniak, Boris A. Malyarchuk, Miroslava V. Derenko, Natasa Kovacevic-Grujicic, Milena Stevanovic, Danijela Drakulic, Slobodan Davidovic, Magdalena Spolnicka, Magdalena Zubanska, Marcin Wozniak
Summary: Data obtained through massive parallel sequencing can be useful in population genetics studies. Machine learning techniques were used in this study to classify DNA samples from Slavic and non-Slavic individuals, with the aim of discerning the genetic provenance of individuals of Slavic descent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Diana Esteller, Marianela Schiava, Rocio-Nur Villar-Quiles, Boris Dibowski, Nadia Venturelli, Pascal Laforet, Jorge Alonso-Perez, Montse Olive, Cristina Dominguez-Gonzalez, Carmen Paradas, Beatriz Velez, Anna Kostera-Pruszczyk, Biruta Kierdaszuk, Carmelo Rodolico, Kristl Claeys, Endre Pal, Edoardo Malfatti, Sarah Souvannanorath, Alicia Alonso-Jimenez, Willem de Ridder, Eline De Smet, George Papadimas, Constantinos Papadopoulos, Sofia Xirou, Sushan Luo, Nuria Muelas, Juan J. Vilchez, Alba Ramos-Fransi, Mauro Monforte, Giorgio Tasca, Bjarne Udd, Johanna Palmio, Srtuhi Sri, Sabine Krause, Benedikt Schoeser, Roberto Fernandez-Torron, Adolfo Lopez de Munain, Elena Pegoraro, Maria Elena Farrugia, Mathias Vorgerd, Georgious Manousakis, Jean Baptiste Chanson, Aleksandra Nadaj-Pakleza, Hakan Cetin, Umesh Badrising, Jodi Warman-Chardon, Jorge Bevilacqua, Nicholas Earle, Mario Campero, Jorge Diaz, Chiseko Ikenaga, Thomas E. Lloyd, Ichizo Nishino, Yukako Nishimori, Yoshihiko Saito, Yasushi Oya, Yoshiaki Takahashi, Atsuko Nishikawa, Ryo Sasaki, Chiara Marini-Bettolo, Michela Guglieri, Volker Straub, Tanya Stojkovic, Robert Y. Carlier, Jordi Diaz-Manera
Summary: By analyzing muscle MRI data from patients with VCP gene mutations, we found that patchy fat replacement and involvement of certain muscles such as the periscapular, paraspinal, gluteal, and quadriceps muscles are common features. These characteristics can be used for accurate diagnosis of VCP disease.
JOURNAL OF NEUROLOGY
(2023)
Meeting Abstract
Clinical Neurology
T. Mozaffar, D. Bratkovic, B. Byrne, K. Claeys, J. Diaz-Manera, P. Kishnani, P. Laforet, M. Roberts, A. Toscano, J. Castelli, M. Goldman, H. Jiang, S. Sitaraman Das, Y. Wasfi, B. Schoser
NEUROMUSCULAR DISORDERS
(2023)
Article
Genetics & Heredity
Joanna Kinga Poninska, Weronika Pelczar-Plachta, Agnieszka Pollak, Katarzyna Jonczyk-Potoczna, Grazyna Truszkowska, Ilona Michalowska, Emilia Szafran, Zofia T. Bilinska, Waldemar Bobkowski, Rafal Ploski
Summary: Familial thoracic aortic aneurysms and dissections in pediatric patients are extremely rare, and there is limited knowledge about the pathogenic variants. This case report presents a 5.5-year-old girl with early-onset aortic aneurysm and concomitant polycystic kidney disease. Whole exome sequencing and family screening identified the presence of two pathogenic variants in the LOX and PKD1 genes in the patient.