Article
Neurosciences
Hasinika K. A. H. Gamage, Katherine J. Robinson, Luan Luu, Ian T. Paulsen, Angela S. Laird
Summary: Emerging evidence suggests bidirectional interactions between the central nervous system and gut microbiota in neurodegenerative diseases, but the role of gut microbes in spinocerebellar ataxia, specifically Machado Joseph disease (MJD), is unknown. This study found sex-specific effects in MJD development and differences in gut microbiota composition between MJD and wild-type mice. The pre-symptomatic microbial changes correlated with the severity of neurological impairments, indicating a potential new target for treating this currently untreatable disease.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Audrius Kilikevicius, Jun Wang, Xiulong Shen, Frank Rigo, Thahza P. Prakash, Marek Napierala, David R. Corey
Summary: This study investigated the potential of using oligonucleotides to increase frataxin expression in a mouse model for Friedreich's ataxia, but found that various mechanisms designed anti-FXN oligonucleotides did not enhance FXN expression in the model mice. The inability to translate activation of FXN expression from cell culture to mice may be due to inadequate potency of the compounds or differences in the molecular mechanisms governing FXN gene repression and activation in the FA model mice.
Article
Neurosciences
Juan Se bastian Martin-Saavedra, Sara Reis Teixeira, Cesar Augusto Pinheiro Ferreira Alves, Fabricio Guimaraes Goncalves, Luis Octavio Tierradentro-Garcia, Martin Kidd, Colleen Muraresku, Amy Goldstein, Arastoo Vossough
Summary: Evaluation of ataxia in children, particularly in primary mitochondrial disorders (PMD), is challenging in clinical practice. This study explored cerebellar and brain abnormalities identified on MRI as potential predictors of ataxia in PMD patients, and determined the effect of genetic profile on these predictors, as well as the temporal relationship of ataxia with MRI findings. The presence of cerebellar atrophy or putaminal involvement with mtDNA mutations, along with nuclear DNA mutations, predicted an increased likelihood of having ataxia per year of age. Central tegmental tract predicted the presence of ataxia independent of age and pathogenic variant origin.
Article
Clinical Neurology
Rino Inada, Makito Hirano, Nobuyuki Oka, Makoto Samukawa, Kazumasa Saigoh, Hidekazu Suzuki, Fukashi Udaka, Akihiro Hashiguchi, Hiroshi Takashima, Yukihiro Hamada, Yusaku Nakamura, Susumu Kusunoki
Summary: This study aimed to clarify the phenotypic and molecular diversities of SCA2 in Japan. Patients with expanded CAG repeats may exhibit a neuropathy-dominant phenotype not previously described. The novel 21-base duplication mutation in Ataxin-2 protein shares aggregation properties with polyglutamine-expanded mutants.
JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Arthavan Selvanathan, Bindu Parayil Sankaran
Summary: Iron-sulfur clusters (ISCs) are highly conserved moieties found in crucial proteins in bacteria, plants and mammals, with defects in the ISC pathway being associated with various human disease states. These disorders often involve neurological phenotypes and share common biochemical features. Therapies are primarily supportive, but improved understanding of the pathophysiology may lead to disease-modifying therapies in the future.
Article
Genetics & Heredity
Satoko Miyatake, Eriko Koshimizu, Atsushi Fujita, Hiroshi Doi, Masaki Okubo, Taishi Wada, Kohei Hamanaka, Naohisa Ueda, Hitaru Kishida, Gaku Minase, Atsuhiro Matsuno, Minori Kodaira, Katsuhisa Ogata, Rumiko Kato, Atsuhiko Sugiyama, Ayako Sasaki, Takabumi Miyama, Mai Satoh, Yuri Uchiyama, Naomi Tsuchida, Haruka Hamanoue, Kazuharu Misawa, Kiyoshi Hayasaka, Yoshiki Sekijima, Hiroaki Adachi, Kunihiro Yoshida, Fumiaki Tanaka, Takeshi Mizuguchi, Naomichi Matsumoto
Summary: We developed a diagnostic method for repeat expansion diseases that is faster, more accurate, and more comprehensive compared to conventional methods.
NPJ GENOMIC MEDICINE
(2022)
Article
Clinical Neurology
Wai Yan Yau, Jana Vandrovcova, Roisin Sullivan, Zhongbo Chen, Anna Zecchinelli, Roberto Cilia, Duga Stefano, Malgorzata Murray, Susana Carmona, Viorica Chelban, Hiroyuki Ishiura, Shoji Tsuji, Zane Jaunmuktane, Chris Turner, Nicholas W. Wood, Henry Houlden
Summary: The prevalence of GGC-repeat expansion in NOTCH2NLC gene in whites with movement disorders is rare, with only a small number of cases identified. Whole-genome sequencing data are valuable for case ascertainment in such studies.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Michael H. Connors, Armando Teixeira-Pinto, Clement T. Loy
Summary: This study examined the longitudinal trajectories and clinical correlates of apathy and depression in patients with Huntington's disease (HD). Apathy increased over time and was associated with worse clinical outcomes, while depression remained relatively stable and had a different set of associations. These findings highlight the importance of distinguishing between apathy and depression in HD.
JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
(2023)
Review
Medicine, General & Internal
Daniele Orsucci, Lucia Lorenzetti, Fulvia Baldinotti, Andrea Rossi, Edoardo Vitolo, Fabio Luigi Gheri, Alessandro Napolitano, Giancarlo Tintori, Marco Vista
Summary: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a premutation in the FMR1 gene. In females, FXTAS has a broad spectrum of symptoms ranging from relatively severe cases starting in mid-adulthood to mild cases beginning in later life.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Terence Gall-Duncan, Nozomu Sato, Ryan K. C. Yuen, Christopher E. Pearson
Summary: Expansions of gene-specific DNA tandem repeats (TRs) have been found to cause more than 60 phenotypes, not just disease, and not only in humans. Technological advances in DNA sequencing and computational analyses have accelerated the discovery of disease-causing TR expansions. From 2019 to 2021, 17 new disease-causing TR expansions were reported, totaling over 69 diseases. Repeat diseases exhibit atypical clinical features, genetic anticipation, and multiple and partially penetrant phenotypes among family members.
Review
Genetics & Heredity
Christel Depienne, Jean-Louis Mandel
Summary: Tandem repeats, a common variation in human genomes, can lead to disorders affecting the central nervous system. While some disorders have been identified, there are still many more to be discovered, and long-read technologies offer a new opportunity for studying these diseases.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Clinical Neurology
Carlo Wilke, David Pellerin, David Mengel, Andreas Traschuetz, Matt C. Danzi, Marie-Josee Dicaire, Manuela Neumann, Holger Lerche, Benjamin Bender, Henry Houlden, Stephan Zuechner, Ludger Schoels, Bernard Brais, Matthis Synofzik
Summary: GAA-FGF14 ataxia is a common late-onset ataxia caused by intronic GAA repeat expansion in the FGF14 gene. This study characterized its phenotypic profile, natural history progression, and treatment response to 4-aminopyridine (4-AP). The results showed that GAA-FGF14 ataxia is typically late-onset with mild progression, and has a positive response to 4-AP treatment.
Article
Clinical Neurology
Friedemann Bender, Dagmar Timmann, Bart P. van de Warrenburg, Astrid D. Adarmes-Gomez, Benjamin Bender, Andreas Thieme, Matthis Synofzik, Ludger Schoels
Summary: The study highlights the rapid progression of polymerase gamma-related ataxia over time, with younger patients showing faster disease progression. The main features include worsening ataxic symptoms and the emergence of non-ataxic characteristics. MRI results indicate structural changes primarily affecting the cerebellum and brainstem regions, alongside abnormal nerve conduction.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Pablo Iruzubieta, David Pellerin, Alberto Bergareche, Ines Albajar, Elisabet Mondragon, Ana Vinagre, Roberto Fernandez-Torron, Fermin Moreno, Jon Equiza, David Campo-Caballero, Juan Jose Poza, Marta Ruibal, Alessandro Formica, Marie-Josee Dicaire, Matt C. Danzi, Stephan Zuchner, Ioana Croitoru, Montserrat Ruiz, Agatha Schluter, Carlos Casasnovas, Aurora Pujol, Bernard Brais, Henry Houlden, Adolfo Lopez de Munain, Javier Ruiz-Martinez
Summary: This study aimed to investigate the frequency and phenotype of SCA27B in patients with unsolved late-onset cerebellar ataxia (LOCA). The results showed that SCA27B is the most common cause of LOCA and screening for FGF14 GAA repeat expansion is recommended as a first-tier genetic test in these patients.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Medical Laboratory Technology
Mulias Lian, Chanin Limwongse, Chui-Sheun Yoon, Caroline G. Lee, Hai-Yang Law, Samuel S. Chong
Summary: This study presents a simplified single-tube assay that can simultaneously screen for CAG repeat expansion in the genes responsible for SCAs 1, 2, 3, 6, 7, 12, and dentatorubral-pallidoluysian atrophy. The method uses differentially labeled locus-specific primers and a common triplet-primed primer to distinguish amplified products from each locus. Blinded evaluation of the assay on 60 genotype-known DNA samples correctly detected repeat expansion in the expected SCA repeat locus for all samples.
CLINICAL CHEMISTRY
(2022)
Article
Clinical Neurology
Resham Ejaz, Shiyi Chen, Charles J. Isaacs, Amanda Carnevale, Judith Wilson, Kristen George, Martin B. Delatycki, Susan L. Perlman, Katherine D. Mathews, George R. Wilmot, J. Chad Hoyle, Sub H. Subramony, Theresa Zesiewicz, Jennifer M. Farmer, David R. Lynch, Grace Yoon
JOURNAL OF CHILD NEUROLOGY
(2018)
Article
Clinical Neurology
Angela J. Lee, Edward T. Buckingham, Aaron J. Kauer, Katherine D. Mathews
JOURNAL OF CHILD NEUROLOGY
(2018)
Article
Clinical Neurology
Maria G. Otero, Emmanuelle Tiongson, Frank Diaz, Katrina Haude, Karin Panzer, Ashley Collier, Jaemin Kim, David Adams, Cynthia J. Tifft, Hong Cui, Francisca Millian Zamora, Margaret G. Au, John M. Graham, David J. Buckley, Richard Lewis, Camilo Toro, Renkui Bai, Lesley Turner, Katherine D. Mathews, William Gahl, Tyler Mark Pierson
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2019)
Correction
Genetics & Heredity
Hernan D. Gonorazky, Sergey Naumenko, Arun K. Ramani, Viswateja Nelakuditi, Pouria Mashouri, Peiqui Wang, Dennis Kao, Krish Ohri, Senthuri Viththiyapaskaran, Mark A. Tarnopolsky, Katherine D. Mathews, Steven A. Moore, Andres N. Osorio, David Villanova, Dwi U. Kemaladewi, Ronald D. Cohn, Michael Brudno, James J. Dowling
AMERICAN JOURNAL OF HUMAN GENETICS
(2019)
Article
Genetics & Heredity
Christoph Bachmann, Faiza Noreen, Nicol C. Voermans, Primo L. Schaer, John Vissing, Johanna M. Fock, Saskia Bulk, Benno Kusters, Steven A. Moore, Alan H. Beggs, Katherine D. Mathews, Megan Meyer, Casie A. Genetti, Giovanni Meola, Rosanna Cardani, Emma Mathews, Heinz Jungbluth, Francesco Muntoni, Francesco Zorzato, Susan Treves
Article
Clinical Neurology
Autumn Rieken, Aaron D. Bossler, Katherine D. Mathews, Steven A. Moore
Summary: FSHD1 accounts for 94.5% of genetically confirmed cases of FSHD. The data show a continuum of D4Z4 repeat numbers with FSHD1 samples having the fewest, FSHD2 an intermediate number, and non-FSHD1,2 the most.
Article
Clinical Neurology
Eric M. Libell, Noelle C. Bowdler, Carrie M. Stephan, Miriam Bridget Zimmerman, Amber M. Gedlinske, Katherine D. Mathews
Summary: This study investigated the experiences and outcomes of pregnancy in women with LGMDR9, finding that most pregnancies were uncomplicated but may require assisted vaginal delivery and could lead to progression of weakness. More research on pregnancy in specific LGMD subtypes is needed to confirm these findings and determine if risks vary by genotype.
Article
Clinical Neurology
Christian Rummey, John M. Flynn, Louise A. Corben, Martin B. Delatycki, George Wilmot, Sub H. Subramony, Khalaf Bushara, Antoine Duquette, Christopher M. Gomez, J. Chad Hoyle, Richard Roxburgh, Lauren Seeberger, Grace Yoon, Katherine D. Mathews, Theresa Zesiewicz, Susan Perlman, David R. Lynch
Summary: Scoliosis is a common comorbidity in patients with Friedreich's ataxia, with early or typical onset patients having a higher risk of developing intermediate to severe scoliosis. Surgical intervention is often needed, especially in the most severe cases, with younger patients delaying surgery until the end of their growth period, leading to further progression of the condition. Age of onset before or after 15 years is a critical factor in determining the severity and progression of scoliosis in FRDA patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Lauren N. Coffey, Carrie M. Stephan, M. B. Zimmerman, Chyan K. Decker, Katherine D. Mathews
Summary: The diagnostic journey for individuals with FKRP mutations in a dystroglycanopathy natural history study was analyzed, revealing that chronic motor dysfunction was the most common initial symptom leading to diagnosis. Some cases were not diagnosed with muscular dystrophy until weakness became apparent. Awareness of disease presentation variability can aid in earlier diagnosis, which is crucial with treatments in development.
NEUROMUSCULAR DISORDERS
(2021)
Article
Pediatrics
Katherine D. Mathews, Kristin M. Conway, Amber M. Gedlinske, Nicholas Johnson, Natalie Street, Russell J. Butterfield, Man Hung, Emma Ciafaloni, Paul A. Romitti
Summary: This study analyzed clinical trial participation among DMD patients and found that fewer non-Hispanic blacks or Hispanics participated in trials compared to non-Hispanic whites, and trial participants tended to reside in counties with lower percentages of non-Hispanic blacks. Understanding these characteristics is important for identifying participation barriers and generalizing trial results.
Article
Clinical Neurology
Richard S. Finkel, Craig M. McDonald, H. Lee Sweeney, Erika Finanger, Erin Neil Knierbein, Kathryn R. Wagner, Katherine D. Mathews, Warren Marks, Jeffrey Statland, Jessica Nance, Hugh J. McMillan, Gary McCullagh, Cuixia Tian, Monique M. Ryan, Declan O'Rourke, Wolfgang Mueller-Felber, Mar Tulinius, W. Bryan Burnette, Cam-Tu Nguyen, Kayal Vijayakumar, Jessika Johannsen, Han C. Phan, Michelle Eagle, James MacDougall, Maria Mancini, Joanne M. Donovan
Summary: Edasalonexent did not show significant improvement in muscle function in DMD patients, but may slow disease progression in younger patients. Most patients tolerated the treatment well with mild adverse events primarily involving the gastrointestinal system.
JOURNAL OF NEUROMUSCULAR DISEASES
(2021)
Article
Clinical Neurology
Naomi Vather-Wu, Matthew D. Krasowski, Katherine D. Mathews, Amal Shibli-Rahhal
Summary: Patients with dystrophinopathies who maintain 25-hydroxyvitamin D levels >= 30 ng/mL on stable doses may only require 25-OHD monitoring every 2-2.5 years, as suggested by the study results.
JOURNAL OF NEUROMUSCULAR DISEASES
(2021)
Article
Genetics & Heredity
Maya Patel, Ashley McCormick, Jaclyn Tamaroff, Julia Dunn, Jonathan A. Mitchell, Kimberly Y. Lin, Jennifer Farmer, Christian Rummey, Susan L. Perlman, Martin B. Delatycki, George R. Wilmot, Katherine D. Mathews, Grace Yoon, Joseph Hoyle, Manuela Corti, S. H. Subramony, Theresa Zesiewicz, David Lynch, Shana E. McCormack
Summary: The study showed that clinical characteristics related to BMI and height in Friedreich ataxia (FRDA) vary among different age groups and sexes, with factors such as age, gender, and disease severity affecting outcomes. These insights will be valuable for assessing affected individuals in research and clinical settings.
NEUROLOGY-GENETICS
(2021)
Article
Clinical Neurology
Anna M. Reelfs, Carrie M. Stephan, Shelley R. H. Mockler, Katie M. Laubscher, M. Bridget Zimmerman, Katherine D. Mathews
Summary: This study found that pain is prevalent in individuals with limb-girdle muscular dystrophy (LGMD) R9, but its impact on daily living and correlation with fatigue remain unknown. Pain interference scores were near normal mean, while fatigue scores were elevated in adults. Pain interference and fatigue were positively correlated. These results suggest that pain in LGMDR9 patients is variable and episodic, with limited impact on daily life, while fatigue increases over time.
NEUROMUSCULAR DISORDERS
(2023)
Article
Genetics & Heredity
Angela J. Lee, Karra A. Jones, Russell J. Butterfield, Mary O. Cox, Chamindra G. Konersman, Carla Grosmann, Jose E. Abdenur, Monica Boyer, Brent Beson, Ching Wang, James J. Dowling, Melissa A. Gibbons, Alison Ballard, Joanne S. Janas, Robert T. Leshner, Sandra Donkervoort, Carsten G. Bonnemann, Denise M. Malicki, Robert B. Weiss, Steven A. Moore, Katherine D. Mathews
NEUROLOGY-GENETICS
(2019)