Article
Genetics & Heredity
Margot A. Cousin, Blake A. Creighton, Keith A. Breau, Rebecca C. Spillmann, Erin Torti, Sruthi Dontu, Swarnendu Tripathi, Deepa Ajit, Reginald J. Edwards, Simone Afriyie, Julia C. Bay, Kathryn M. Harper, Alvaro A. Beltran, Lorena J. Munoz, Liset Falcon Rodriguez, Michael C. Stankewich, Richard E. Person, Yue Si, Elizabeth A. Normand, Amy Blevins, Alison S. May, Louise Bier, Vimla Aggarwal, Grazia M. S. Mancini, Marjon A. van Slegtenhorst, Kirsten Cremer, Jessica Becker, Hartmut Engels, Stefan Aretz, Jennifer J. MacKenzie, Eva Brilstra, Koen L. I. van Gassen, Richard H. van Jaarsveld, Renske Oegema, Gretchen M. Parsons, Paul Mark, Ingo Helbig, Sarah E. McKeown, Robert Stratton, Benjamin Cogne, Bertrand Isidor, Pilar Cacheiro, Damian Smedley, Helen V. Firth, Tatjana Bierhals, Katja Kloth, Deike Weiss, Cecilia Fairley, Joseph T. Shieh, Amy Kritzer, Parul Jayakar, Evangeline Kurtz-Nelson, Raphael A. Bernier, Tianyun Wang, Evan E. Eichler, Ingrid M. B. H. van de Laar, Allyn McConkie-Rosell, Marie T. McDonald, Jennifer Kemppainen, Brendan C. Lanpher, Laura E. Schultz-Rogers, Lauren B. Gunderson, Pavel N. Pichurin, Grace Yoon, Michael Zech, Robert Jech, Juliane Winkelmann, Adriana S. Beltran, Michael T. Zimmermann, Brenda Temple, Sheryl S. Moy, Eric W. Klee, Queenie K. -G. Tan, Damaris N. Lorenzo
Summary: SPTBN1 mutations cause a neurodevelopmental syndrome with intellectual disability, language and motor delays, and other features. Heterozygous SPTBN1 variants disrupt beta II-spectrin stability, binding to molecular partners, and disturb cytoskeleton organization and dynamics, suggesting compromise of neural development and function. This study expands the understanding of spectrinopathies affecting the brain and highlights the critical role of beta II-spectrin in the central nervous system.
Article
Cell Biology
Huan-Yun Chen, Chia-Lang Hsu, Han-Yi Lin, Yung-Feng Lin, Shih-Feng Tsai, Yu-Jung Ho, Ye-Ru Li, Jin-Wu Tsai, Shu-Chun Teng, Chin-Hsien Lin
Summary: A novel heterozygous frameshift variant in the STUB1 gene was identified in Taiwanese patients with autosomal dominant cerebellar ataxia, leading to the onset of SCA48. This mutation impairs the activity of the CHIP protein, causing neuronal protein accumulation and apoptosis, highlighting the importance of neuronal protein homeostasis in this disease. These findings offer insight into the pathogenesis of SCA48 and emphasize the role of CHIP activity in cerebellar functions.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Review
Clinical Neurology
Giulia Coarelli, Marie Coutelier, Alexandra Durr
Summary: Dominantly inherited spinocerebellar ataxias (SCAs) exhibit phenotypic variation and can be caused by multiple potentially pathogenic variants. Genome sequencing should be the preferred diagnostic tool due to the extreme clinical and genetic heterogeneity, but its availability is limited. Although treatments like riluzole and transcranial direct current stimulation have been tested, their efficacy remains conflicting. Biomarkers, such as neurofilament light chain and brain MRI, should be used to assess preataxic carriers and monitor target engagement by gene therapies.
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)
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
Neurosciences
Vito Luigi Colona, Enrico Bertini, Maria Cristina Digilio, Adele D'Amico, Antonio Novelli, Stefano Pro, Elisa Pisaneschi, Francesco Nicita
Summary: POLR3B gene encodes the RPC2 subunit of RNA polymerase III, and pathogenic variants are associated with various disorders, including hypomyelinating leukodystrophy and Charcot-Marie-Tooth syndrome type 1I. In this study, a new variant in the POLR3B gene was identified in a patient with developmental delay, epilepsy, and polyneuropathy.
Review
Neurosciences
Ziwei Gong, Lifang Lei
Summary: Spinocerebellar ataxias, also known as autosomal dominant cerebellar ataxias, are genetic diseases characterized by chronic cerebellar ataxia. Spinocerebellar ataxia type 11 is a rare subtype caused by mutations in the tau tubulin kinase 2 gene. This article discusses a series of spinocerebellar ataxia cases, including epidemiology, clinical features, genetics, diagnosis, pathogenic mechanisms, treatment, prognosis, follow-up, genetic counseling, and future perspectives, aiming to improve the overall understanding of spinocerebellar ataxia among clinicians, researchers, and patients.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
Sohaila Alshimemeri, Danah Abo Alsamh, Lily Zhou, Sarah Furtado, Scott Kraft, Veronica Bruno, Antoine Duquette, Bernard Brais, Oksana Suchowersky, Renato P. P. Munhoz, Elizabeth Slow
Summary: This study reports the epidemiological and clinical characteristics of patients with autosomal dominant spinocerebellar ataxias (AD SCA) in Canada. The distribution of the most common SCA types differed among the three provinces studied, reflecting the heterogenous nature of the Canadian population.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Wladimir Bocca Vieira de Rezende Pinto, Rubens Paulo Araujo Saloma, Nathlia Carbral Bergamsco, Gustavo da Cunha Ribas, Felipe Franco da Graca, Iscia Lopez-Cendes, Luciana Bonadia, Paulo Victor Sgobbi de Souza, Acary Souza Bulle Oliveira, Maria Luiza Saraiva-Perira, Laura Bannach Jardin, Vitor Tumas, Wilson Marques Jr, Marcondes C. Franca Jr, Jose Luiz Pedroso, Orlando G. P. Barsottini, Helio A. G. Teive
Summary: This study describes the clinical features of DRPLA in Brazilian patients, highlighting the influence of age of onset, genetic anticipation, and CAG repeat lengths on the disease. The study also emphasizes the wide spectrum of neurological features associated with DRPLA, ranging from pure cerebellar ataxia to dementia with other movement disorders. DRPLA is an uncommon cause of cerebellar ataxia and neurodegeneration in Brazilian patients.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Yannic Saathoff, Saskia Biskup, Claudia Funke, Christian Roth
Summary: Genetic testing for hereditary ataxias plays a crucial role in diagnosis and understanding of familial genetic diseases. Identification of novel pathogenic variants in a patient highlights the importance of understanding their inheritance patterns for the treatment and prevention of familial genetic disorders.
JOURNAL OF MOVEMENT DISORDERS
(2021)
Article
Geriatrics & Gerontology
Hui Chen, Limeng Dai, Yuhan Zhang, Liu Feng, Zhenzhen Jiang, Xingang Wang, Dongjing Xie, Jing Guo, Huafu Chen, Jian Wang, Chen Liu
Summary: This study used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the brain network in patients with Spinocerebellar ataxia type 3 (SCA3). The results showed that the brain networks tended to be more regular in SCA3 patients, with reorganization in motor and visual-related areas. These findings provide new insights into the neurological mechanisms underlying SCA3 network topology impairments in the resting state.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Clinical Neurology
Raquel Baviera-Munoz, Lidon Carretero-Vilarroig, Nuria Muelas, Rafael Sivera, Pablo Sopena-Novales, Begona Martinez-Sanchis, Isabel Sastre-Bataller, Marina Campins-Romeu, Irene Martinez-Torres, Jose Manuel Garcia-Verdugo, Jose M. Millan, Teresa Jaijo, Elena Aller, Luis Bataller
Summary: SCA36 is a common cause of hereditary ataxia in Eastern Spain, with a strong founder effect. Its clinical features include hypoacusis, pyramidal signs, lingual fasciculations/atrophy, dystonia, and parkinsonism. SCA36 analysis should be considered as a priority in the study of hereditary ataxia, especially in patients with late onset.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Marise Bueno Zonta, Helio A. G. Teive, Carlos Henrique F. Camargo, Alex T. Meira, Francisco Diego Negrao Lopes Neto, Fernando Spina Tensini, Claudia Bonfim Braga, Tetsuo Ashizawa, Renato P. Munhoz
Summary: The progression of spinocerebellar ataxia varies depending on the subtype and disease course. SCA3 shows a more linear and aggressive progression compared to SCA2 and SCA10, which exhibit non-linear patterns. The rate of decline in balance and independence of daily activities is faster in SCA3 compared to the other subtypes.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2022)
Article
Chemistry, Medicinal
Tomonori Shibata, Kazuhiko Nakatani
Summary: Spinocerebellar ataxia type 31 is a genetic neurodegenerative disease caused by an aberrant insertion of d(TGGAA)n on chromosome 16. Our study found that a naphthyridine dimer derivative with an amidated linker structure (ND-amide) specifically bound to GGA/GGA motifs in hairpin structures of d(TGGAA)n. The binding affinity was influenced by the linker structure, and amidation of the linker improved the binding to GGA/GGA motifs compared to non-amidated naphthyridine dimer.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Rehabilitation
Stanley Winser, Ho Kwan Chan, Wing Ki Chen, Chung Yau Hau, Siu Hang Leung, Kimmy Yh Leugn, Umar Muhammad Bello
Summary: This study reviewed the benefits of therapeutic exercises in cerebellar ataxia patients. The results showed that therapeutic exercises can reduce disease severity and improve balance, but have no significant effect on functional independence. More high-quality studies are needed to further confirm these findings.
PHYSIOTHERAPY THEORY AND PRACTICE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Annemieke Aartsma-Rus, Willeke van Roon-Mom, Marlen Lauffer, Christine Siezen, Britt Duijndam, Tineke Coenen-de Roo, Rebecca Schuele, Matthis Synofzik, Holm Graessner
Summary: Splice-modulating antisense oligonucleotides (ASOs) provide treatment options for rare neurological diseases with rare mutations, and patient-specific ASOs need to be developed. The 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop and treat eligible patients with patient-specific ASOs in Europe and the Netherlands, respectively, under a named patient setting.
Article
Neurosciences
Wolfram Ziegler, Theresa Schoelderle, Bettina Brendel, Verena Risch, Stefanie Felber, Katharina Ott, Georg Goldenberg, Mathias Vogel, Kai Boetzel, Lena Zettl, Stefan Lorenzl, Renee Lampe, Katrin Strecker, Matthis Synofzik, Tobias Lindig, Hermann Ackermann, Anja Staiger
Summary: This study investigated the relationship between commonly used nonspeech parameters in clinical dysarthria assessment and the speech characteristics of dysarthria in individuals with movement disorders. The findings suggest that the nonspeech parameters currently used in dysarthria diagnostics do not align with diagnostic measures of speech characteristics in individuals with dysarthria.
Article
Biochemistry & Molecular Biology
Tama Dinur, Peter Bauer, Christian Beetz, Claudia Cozma, Michal Becker-Cohen, Majdolen Istaiti, Arndt Rolfs, Volha Skrahina, Ari Zimran, Shoshana Revel-Vilk
Summary: Glucosylsphingosine (lyso-Gb1), the deacylated form of glucocerebroside, is a specific and sensitive biomarker for diagnosing Gaucher disease (GD). This study assessed the impact of lyso-Gb1 levels at the time of diagnosis on treatment decisions in newly diagnosed GD patients. The findings suggest that higher lyso-Gb1 levels are associated with the initiation of GD-specific therapy, especially among mildly affected patients. However, the exact cutoff value may vary due to differences in measurement methodologies and units between laboratories.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medical Laboratory Technology
P. Mihika S. Fernando, R. A. Saraji R. Gunasekara, Sabine Schroeder, Christian Beetz, Anura Jayawardena, Eresha A. Jasinge
LABORATORY MEDICINE
(2023)
Article
Health Care Sciences & Services
M. Grobe-Einsler, J. Faber, A. Taheri, J. Kybelka, J. Raue, J. Volkening, F. Helmhold, M. Synofzik, T. Klockgether
Summary: Ataxias refer to a group of movement disorders, characterized by progressive loss of balance, impaired coordination, and speech disturbance, resulting in a significant reduction in quality of life. Although speech disturbance can be clinically diagnosed, there is a lack of objective methods for assessing its severity. Through the analysis of 71 sets of speech recordings from ataxia patients, an automated classification system was developed. This system correctly predicted the expert ratings of speech disturbance in 80% of cases, demonstrating the feasibility of computer-assisted voice analysis for automated assessment of speech disturbance severity.
NPJ DIGITAL MEDICINE
(2023)
Letter
Clinical Neurology
Holger Hengel, David Pellerin, Carlo Wilke, Zofia Fleszar, Bernard Brais, Tobias Haack, Andreas Traschuetz, Ludger Schoels, Matthis Synofzik
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Andreas Traschuetz, Felix Heindl, Muhammad Bilal, Annette M. Hartmann, Claudia Dufke, Olaf Riess, Andreas Zwergal, Dan Rujescu, Tobias Haack, Matthis Synofzik, Michael Strupp
Summary: Bilateral vestibulopathy is a chronic neurological disorder with unknown monogenic cause. This study identifies replication factor complex subunit 1 repeat expansions as a common cause of the disease and provides detailed characterization of its features and progression.
Article
Biology
Federico Zilio, Javier Gomez-Pilar, Ujwal Chaudhary, Stuart Fogel, Tatiana Fomina, Matthis Synofzik, Ludger Schols, Shumei Cao, Jun Zhang, Zirui Huang, Niels Birbaumer, Georg Northoff
Summary: EEG-based measures such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) can be used to identify biomarkers associated with complete locked-in syndrome (CLIS), allowing for better treatment and communication options.
COMMUNICATIONS BIOLOGY
(2023)
Article
Clinical Neurology
Arian Taheri Amin, Jennifer Faber, Demet Onder, Okka Kimmich, Matthis Synofzik, Tetsuo Ashizawa, Thomas Klockgether, Marcus Grobe-Einsler
Summary: After conducting comprehensive SARA assessments on video recordings of 69 patients with cerebellar ataxia, it was found that there was a high level of agreement between live ratings by site investigators and remote video ratings by experienced ataxia clinicians, indicating that remote video ratings are a reliable means to assess the severity of ataxia.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Catherine Ashton, Elisabetta Indelicato, David Pellerin, Guillemette Clement, Matt C. Danzi, Marie-Josee Dicaire, Celine Bonnet, Henry Houlden, Stephan Zuechner, Matthis Synofzik, Phillipa J. Lamont, Mathilde Renaud, Sylvia Boesch, Bernard Brais
Summary: Ashton C et al report a retrospective multi-centre cohort study of 34 patients from Canada, France, Austria and Australia with spinocerebellar ataxia 27B. The study describes the common feature of episodic ataxia and other episodic features, and also highlights the ineffectiveness of acetazolamide in these patients.
BRAIN COMMUNICATIONS
(2023)
Article
Neurosciences
Filippo Santorelli, Hayley McLoughlin, Justin Wolter, Daniele Galatolo, Matthis Synofzik, David Mengel, Puneet Opal
Summary: The Ataxia Global Initiative (AGI) aims to facilitate clinical trial readiness for hereditary ataxias by addressing the lack of objective measures for disease study and treatment evaluation. The AGI fluid biomarker working group has developed protocols to standardize sampling and storage of biomarkers for both human and mouse studies, with the goal of reducing variability and improving statistical power in downstream analysis. Emphasis has been placed on harmonizing minimal biological sample collection and storage, while optional protocols are available for advanced biofluid processing and storage.
Correction
Clinical Neurology
Holger Hengel, Peter Martus, Jennifer Faber, Paola Giunti, Hector Garcia-Moreno, Nita Solanky, Thomas Klockgether, Kathrin Reetz, Bart P. van de Warrenburg, Magda M. Santana, Patrick Silva, Ines Cunha, Luis Pereira de Almeida, Dagmar Timmann, Jon Infante, Jeroen de Vries, Manuela Lima, Paula Pires, Khalaf Bushara, Heike Jacobi, Chiadi Onyike, Jeremy D. Schmahmann, Jeannette Huebener-Schmid, Matthis Synofzik, Ludger Schoels
JOURNAL OF NEUROLOGY
(2023)
Article
Genetics & Heredity
Sandra Martins, Ashraf Yahia, Ines P. D. Costa, Hassab E. Siddig, Rayan Abubaker, Mahmoud Koko, Marc Corral-Juan, Antoni Matilla-Duenas, Alexis Brice, Alexandra Durr, Eric Leguern, Laura P. W. Ranum, Antonio Amorim, Liena E. O. Elsayed, Giovanni Stevanin, Jorge Sequeiros
Summary: Machado-Joseph disease (MJD/SCA3) is the most common dominant ataxia worldwide, caused by a (CAG)n expansion. This study reports the first diagnosed MJD case in Sudan, with genetic analysis revealing shared ancestry with Portuguese, Spanish, and North American families. The STR-based haplotype of the Sudanese patients is distinct, indicating a unique genetic background.
Article
Neurosciences
Maresa Buchholz, Niklas Weber, Anika Raedke, Jennifer Faber, Tanja Schmitz-Huebsch, Heike Jacobi, Feng Xie, Thomas Klockgether, Bernhard Michalowsky
Summary: The study confirmed an acceptable, reliable, valid, and responsive EQ-5D-3L in SCA patients, measuring HRQoL adequately, besides well-established clinical instruments.