Article
Clinical Neurology
Han-Lin Chiang, Jong-Ling Fuh, Yu-Shuen Tsai, Bing-Wen Soong, Yi-Chu Liao, Yi-Chung Lee
Summary: Mutations in the AFG3L2 gene can cause a broad spectrum of diseases, including SCA28 and SPAX5. This study identified a patient with compound heterozygous mutations in AFG3L2, expanding the clinical spectrum and suggesting a new subtype of late-onset SCAR.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Genetics & Heredity
Kari J. Ekenstedt, Katie M. Minor, G. Diane Shelton, James J. Hammond, Andrew D. Miller, Susan M. Taylor, Yanyun Huang, James R. Mickelson
Summary: ARSACS is a human neurological disorder characterized by progressive cerebellar ataxia and peripheral neuropathy. A similar disorder was recently identified in Great Pyrenees dogs, showing widespread central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. The disease follows an autosomal recessive inheritance pattern and is associated with mutations in the SACS gene.
Article
Clinical Neurology
Natasa Dragasevic-Miskovic, Iva Stankovic, Andona Milovanovic, Vladimir S. Kostic
Summary: Autosomal recessive ataxias (ARCA) encompass a wide range of diseases, from primary ataxias to complex metabolic disorders where ataxia is just one aspect. Proper differential diagnosis is crucial for adult-onset ARCA, as they may be treatable and have prognostic implications.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Anthony J. Linares, Brent L. Fogel
Summary: Late-onset genetic cerebellar ataxias are clinically heterogenous and can present with variable phenotypes, including dementia. Understanding the relationship between ataxia and dementia can guide clinical genetic evaluation.
CURRENT OPINION IN NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yasaman Pakdaman, Siren Berland, Helene J. Bustad, Sigrid Erdal, Bryony A. Thompson, Paul A. James, Kjersti N. Power, Stale Ellingsen, Martin Krooni, Line I. Berge, Adrienne Sexton, Laurence A. Bindoff, Per M. Knappskog, Stefan Johansson, Ingvild Aukrust
Summary: Variants in STUB1 can cause both autosomal recessive SCAR16 and dominant SCA48, with novel dominantly inherited STUB1 variants in patients showing symptoms after 30 years of age, cerebellar atrophy, and cognitive/psychiatric phenotypes. Studies on the molecular properties of these dominant variants revealed impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP, expanding the understanding of SCA48 and suggesting a need for re-evaluation of assumptions about unaffected carriers of recessive STUB1 variants in SCAR16 families. Further investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Marie Beaudin, Mario Manto, Jeremy D. Schmahmann, Massimo Pandolfo, Nicolas Dupre
Summary: In this Review, the authors discuss recessive ataxias with ganglionopathy or polyneuropathy, focusing on Friedreich ataxia and RFC1-associated cerebellar ataxia, neuropathy, vestibular areflexia syndrome. They explore the shared pathogenic mechanisms and therapeutic advances in these diseases. The Review also provides insights into the diagnostic challenges and clinical features of these diseases.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Neurosciences
William Kristian Karlsson, Joan Lilja Sunnleyg Hojgaard, Anna Vilhelmsen, Clarissa Crone, Birgit Andersen, Ian Law, Lisbeth Birk Moller, Troels Tolstrup Nielsen, Emilie Neerup Nielsen, Thomas Krag, Kirsten Svenstrup, Jorgen Erik Nielsen
Summary: Pathogenic variants in the SYNE1 gene can lead to a range of symptoms from pure ataxia to multisystemic disease. This case study presents a novel homozygous truncating variant in the SYNE1 gene in a 20-year-old female patient with early-onset cerebellar deficits, motor neuron involvement, and cognitive deficits, expanding the understanding of the phenotypic spectrum associated with SYNE1 mutations. The findings also reveal unique neuroimaging and electrophysiological abnormalities that further characterize the disease presentation.
Article
Genetics & Heredity
Nannan Qian, Taohua Wei, Wenming Yang, Jiuxiang Wang, Shijie Zhang, Shan Jin, Wei Dong, Wenjie Hao, Yue Yang, Ru Huang
Summary: ARCA-1 (or SCAR8) is a hereditary cerebellar ataxia caused by SYNE1 gene mutation. Its clinical features are primarily characterized by cerebellar ataxia and may be accompanied by upper and/or lower motor neuron dysfunction.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Milla-Riikka Hautakangas, Paula Widgren, Paavo Korpelainen, Salla M. Kangas, Tuomas Komulainen, Paivi Vieira, Elisa Rahikkala, Katri Pylkas, Hannu Tuominen, Hannaleena Kokkonen, Ilkka Miinalainen, Javad Nadaf, Jacek Majewski, Reetta Hinttala, Johanna Uusimaa
Summary: We studied a patient with a unique mitochondrial DNA depletion syndrome characterized by various organ impairments. We identified a previously unpublished variant in the DHX16 gene, which is known to cause neuromuscular oculoauditory syndrome. Functional studies on patient-derived cells revealed decreased expression of DHX16. Our findings suggest that the novel DHX16 variant is responsible for the patient's disease and that mitochondrial DNA depletion may be a secondary manifestation.
Article
Clinical Neurology
Tanja Schmitz-Huebsch, Silke Lux, Peter Bauer, Alexander U. Brandt, Elena Schlapakow, Susanne Greschus, Michael Scheel, Hanna Gaertner, Mehmet E. Kirlangic, Vincent Gras, Dagmar Timmann, Matthis Synofzik, Alejandro Giorgetti, Paolo Carloni, Jon N. Shah, Ludger Schoels, Ute Kopp, Lisa Bussenius, Timm Oberwahrenbrock, Hanna Zimmermann, Caspar Pfueller, Ella-Maria Kadas, Maria Roennefarth, Anne-Sophie Grosch, Matthias Endres, Katrin Amunts, Friedemann Paul, Sarah Doss, Martina Minnerop
Summary: Genetic variant classification presents a challenge in rare adult-onset disorders like SCA-PRKCG, which has private conventional mutations and nonspecific phenotypes. This study proposes a refined approach for clinicogenetic diagnosis, including protein modeling, and provides a comprehensive phenotype description for confirmed cases, along with a novel T2 hyperintense dentate sign as a potential diagnostic marker.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Genetics & Heredity
Marianne Majdalani, Nadine Yazbeck, Lamis El Harake, Jinane Samaha, Pascale E. E. Karam
Summary: This article describes a rare disorder called mitochondrial DNA depletion syndrome type 3, which is linked to variants in the deoxyguanosine kinase gene. The disorder is frequent in the Middle East and North Africa, and diagnosis is often delayed due to nonspecific clinical presentation. Liver transplantation is currently the only therapeutic option. The study presents the clinical, biochemical, and molecular profiles of Lebanese patients with this disorder, as well as a review of cases from the Middle East and North Africa.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
Giovanna De Michele, Daniele Galatolo, Serena Galosi, Andrea Mignarri, Gabriella Silvestri, Carlo Casali, Vincenzo Leuzzi, Ivana Ricca, Melissa Barghigiani, Alessandra Tessa, Ettore Cioffi, Caterina Caputi, Vittorio Riso, Maria Teresa Dotti, Francesco Sacca, Giuseppe De Michele, Sirio Cocozza, Alessandro Filla, Filippo M. Santorelli
Summary: This study identified fourteen patients in ten families with nine pathogenic heterozygous variants in PRKCG, expanding the spectrum of SCA14 in terms of both genetics and clinical manifestations. The novel variants discovered in this study contribute to a better understanding of the disease and its phenotypic variability.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
V Montano, D. Orsucci, V Carelli, C. La Morgia, M. L. Valentino, C. Lamperti, S. Marchet, O. Musumeci, A. Toscano, G. Primiano, F. M. Santorelli, C. Ticci, M. Filosto, A. Rubegni, T. Mongini, P. Tonin, S. Servidei, R. Ceravolo, G. Siciliano, Michelangelo Mancuso
Summary: The study reviewed the prevalence and clinical features of movement disorders in adults with primary mitochondrial diseases of the Italian Collaborative Network of Mitochondrial Diseases. It emphasizes the importance of considering a mitochondrial etiology in the diagnostic flowchart of a movement disorder.
JOURNAL OF NEUROLOGY
(2022)
Article
Genetics & Heredity
Haloom Rafehi, Justin Read, David J. Szmulewicz, Kayli C. Davies, Penny Snell, Liam G. Fearnley, Liam Scott, Mirja Thomsen, Greta Gillies, Kate Pope, Mark F. Bennett, Jacob E. Munro, Kathie J. Ngo, Luke Chen, Mathew J. Wallis, Ernest G. Butler, Kishore R. Kumar, Kathy H. C. Wu, Susan E. Tomlinson, Stephen Tisch, Abhishek Malhotra, Matthew Lee-Archer, Egor Dolzhenko, Michael A. Eberle, Leslie J. Roberts, Brent L. Fogel, Norbert Bruggemann, Katja Lohmann, Martin B. Delatycki, Melanie Bahlo, Paul J. Lockhart
Summary: This study identified an intronic (GAA) repeat expansion in FGF14 and demonstrated that (GAA)>335 is a disease-causing variant while (GAA)>250 is likely pathogenic. Affected individuals presented with adult-onset cerebellar ataxia with variable features.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Tina Harmuth, Jonasz J. Weber, Anna J. Zimmer, Anna S. Sowa, Jana Schmidt, Julia C. Fitzgerald, Ludger Schoels, Olaf Riess, Jeannette Huebener-Schmid
Summary: Dysfunctional mitochondria are associated with various neurodegenerative diseases, including SCA3. This study reveals impaired mitochondrial function and mitophagy in SCA3 patient cells, as well as inhibited deubiquitination of VDAC1 and recruitment of parkin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Jenni M. Lehtonen, Mari Auranen, Niklas Darin, Kalliopi Sofou, Laurence Bindoff, Omar Hikmat, Johanna Uusimaa, Paivi Vieira, Mar Tulinius, Tuula Lonnqvist, Irenaeus F. de Coo, Anu Suomalainen, Pirjo Isohanni
Summary: The study demonstrates that in the diagnosis of mitochondrial disease, the value of serum biomarkers FGF21 and GDF15 is higher than traditional muscle histological analysis. Additionally, if both biomarkers are elevated and the patient exhibits muscle manifesting symptoms and is affected by mitochondrial DNA expression, the likelihood of diagnosing mitochondrial disease is higher.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Medicine, Legal
Utsav Parekh, Patrick Chariot, Catherine Dang, Arne Stray-Pedersen, Henrik Druid, Antti Sajantila
JOURNAL OF FORENSIC AND LEGAL MEDICINE
(2020)
Article
Cell Biology
Steffi Goffart, Petra Tikkanen, Craig Michell, Trevor Wilson, Jaakko L. O. Pohjoismaki
Summary: This study found that different oxidants elicit different responses in HEK293T cells, and acute oxidative stress does not universally induce DNA repair or antioxidant defense mechanisms. Additionally, cells previously exposed to oxidative stress show adaptive changes in their responses when stress is renewed.
Article
Cardiac & Cardiovascular Systems
Annu Nummi, Severi Mulari, Juhani A. Stewart, Sari Kivisto, Kari Teittinen, Tuomo Nieminen, Milla Lampinen, Tommi Patila, Harri Sintonen, Tatu Juvonen, Markku Kupari, Raili Suojaranta, Esko Kankuri, Ari Harjula, Antti Vento
Summary: The epicardial transplantation of atrial appendage micrografts during CABG surgery was shown to be safe and feasible, resulting in an increase in viable cardiac tissue at the infarct site. This approach demonstrated initial therapeutic effects on the myocardium and has the potential to serve as a delivery platform for cardiac gene therapies.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Endocrinology & Metabolism
Selma L. van Esveld, Richard J. Rodenburg, Fathiya Al-Murshedi, Eiman Al-Ajmi, Sana Al-Zuhaibi, Martijn A. Huynen, Johannes N. Spelbrink
Summary: In this study, two patients with a mutation in the SUPV3L1 gene were reported. They showed a neurodegenerative phenotype characterized by progressive spastic paraparesis, growth restriction, hypopigmentation, and predisposition to autoimmune disease. The mutation resulted in reduced expression of the truncated protein, decreased levels of mature mRNA, and accumulation of double-stranded RNA. Lentiviral complementation with the full-length SUPV3L1 gene partially restored the RNA abnormalities, indicating that the mutation is pathogenic and causes the disease.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Virology
Outi I. Mielonen, Diogo Pratas, Klaus Hedman, Antti Sajantila, Maria F. Perdomo
Summary: This study evaluated the sensitivity of viral detection in lung, liver, and kidney specimens under formalin fixation conditions. It was found that formalin fixation can hinder nucleic acid screening, especially for low-abundance DNA viruses. However, low-copy viral DNA can still be satisfactorily investigated from formalin-fixed, paraffin-embedded (FFPE) specimens with appropriate extraction methods.
Article
Multidisciplinary Sciences
Jessica W. Luzwick, Eszter Dombi, Rebecca A. Boisvert, Sunetra Roy, Soyoung Park, Selvi Kunnimalaiyaan, Steffi Goffart, Detlev Schindler, Katharina Schlacher
Summary: The Fanconi anemia suppressor genes in mitochondria protect mtDNA replication forks, while degradation by MRE11 nuclease leads to loss of nascent mtDNA. Unlike nuclear DNA replication fork stability, mitochondrial replication fork protection does not require pathway activation, revealing a separation between the two stability pathways.
Article
Cardiac & Cardiovascular Systems
Severi Mulari, Arda Eskin, Milla Lampinen, Annu Nummi, Tuomo Nieminen, Kari Teittinen, Teija Ojala, Matti Kankainen, Antti Vento, Jari Laurikka, Markku Kupari, Ari Harjula, Nurcan Tuncbag, Esko Kankuri
Summary: This study identified signature RNAs associated with ischemic heart disease from the atrial myocardium, showing repression of RNA expression in pathways for cell-cell contacts and mitochondrial dysfunction. Increased expressions of specific genes were correlated with the severity of coronary artery obstructions or functional benefits from cardiac bypass surgery.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Engineering, Aerospace
Tanja Laukkala, Eero Pukkala, Bruce Budowle, Antti Sajantila, Matti Mantysaar, Heini Huhtala, Alpo Vuorio
Summary: This study focuses on Vietnam War pilots and subsequent fatal aviation accidents in the U.S from 1965 to 2018. A total of nine aviation accidents met the inclusion criteria and are described in detail, including the pilots' previous civil aviation incidents. Although the data are limited, this study suggests that previous military pilots may differ slightly from other pilots in their subsequent civil aviation careers.
Article
Biochemistry & Molecular Biology
Jussi Leinonen, Paivi Leinikka, Miikka Tarkia, Milla Lampinen, Avishag K. Emanuelov, Ronen Beeri, Esko Kankuri, Eero Mervaala
Summary: The left atrial appendage (LAA) of the adult heart contains progenitor cells and can be used as a regenerative transplant for myocardial infarction. Transplantation of LAA to mice with MI resulted in improved cardiac function and inhibition of deleterious remodeling. This method combines cell therapy and physical support.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anu Hangas, Nina J. Kekalainen, Alisa Potter, Craig Michell, Kauko J. Aho, Chiara Rutanen, Johannes N. Spelbrink, Jaakko L. Pohjoismaki, Steffi Goffart
Summary: This study investigates the role of Topoisomerase 3 alpha (Top3 alpha) in mitochondrial DNA (mtDNA) replication and transcription. The findings suggest that Top3 alpha not only participates in mtDNA segregation but also supports the progression of the replication fork. Knockdown of Top3 alpha leads to replication fork stalling, increased mtDNA catenation, and decreased mtDNA levels. Overexpression, on the other hand, induces double-strand breaks and early replication termination while improving the resolution of mtDNA replication termination intermediates. Both knockdown and overexpression of Top3 alpha affect mitochondrial RNA transcription, resulting in a decrease in steady-state levels of mitochondrial transcripts.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Annu Nummi, Tommi Patila, Severi Mulari, Milla Lampinen, Tuomo Nieminen, Mikko Mayranpaa, Antti Vento, Ari Harjula, Esko Kankuri
Summary: Epicardial transplantation of autologous atrial appendage micrografts (AAMs) is a feasible and safe therapy for heart failure, which can inhibit the inflammatory response induced by extracellular matrix (ECM) patches on the epicardium.
SCANDINAVIAN CARDIOVASCULAR JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Lari Pyoria, Diogo Pratas, Mari Toppinen, Klaus Hedman, Antti Sajantila, Maria F. Perdomo
Summary: This study revealed the genetic composition and unique makeup of known eukaryotic human DNA viruses in different organs, and found unprecedented prevalences of viral DNAs in human organs. The findings provide fundamental knowledge for investigating the correlation between viruses and diseases.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Alpo Vuorio, Robert Bor, Antti Sajantila, Anna-Stina Suhonen-Malm, Bruce Budowle
Summary: Based on the analysis of four accidents involving commercial aircraft-assisted suicides, it is found that examining the mental health of pilots and conducting detailed psychological autopsy can effectively reduce suicidal acts in commercial aircraft accidents.
Article
Biochemistry & Molecular Biology
Koit Aasumets, Yuliya Basikhina, Jaakko L. Pohjoismaki, Steffi Goffart, Joachim Gerhold
Summary: The correct organization of mitochondrial DNA and the contacts of mitochondria with the ER are crucial for maintaining mitochondrial genome distribution within the cell. Knockdown of TFAM, a core component of mitochondrial nucleoids, results in changes in nucleoid populations, impacting ER-mitochondria membrane contacts. On the other hand, knockdown of the mitochondrial replicative helicase TWNK affects mtDNA copy number and membrane association, without causing nucleoid aggregation or notable alterations in MAM proteins.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2021)