Article
Genetics & Heredity
Elena Panzeri, Andrea Citterio, Andrea Martinuzzi, Vera Ancona, Eleonora Martini, Maria Teresa Bassi
Summary: In this study, an 8-year-old patient with severe and complicated spastic paraplegia was found to carry a missense variant and a novel intragenic deletion in the FARS2 gene. The disease in this patient progressed rapidly and in a biphasic way, which differs from previously reported cases. This study provides a detailed molecular characterization of a FARS2 deletion and highlights the importance of combining different tools to improve the diagnostic rate.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Parizad Varghaei, Grace Yoon, Mehrdad A. Estiar, Simon Veyron, Etienne Leveille, Nicolas Dupre, Jean-Francois Trempe, Guy A. Rouleau, Ziv Gan-Or
Summary: GCH1 mutations may cause hereditary spastic paraplegia (HSP), suggesting a levodopa trial in HSP patients and including GCH1 in the screening panels of HSP genes. Clinical differences between monozygotic twins suggest that environmental factors, epigenetics, and stochasticity could play a role in the clinical presentation.
Article
Genetics & Heredity
Shan-Yu Gao, Yu-Xing Liu, Yi Dong, Liang-Liang Fan, Qi Ding, Lv Liu
Summary: In this study, a novel splice-altering variant in the WASHC5 gene was identified in a Chinese family with HSP. Genetic sequencing and RNA splicing analysis provided evidence linking this variant to the pathogenesis of HSP, offering valuable genetic counseling information to the family.
FRONTIERS IN GENETICS
(2023)
Letter
Clinical Neurology
J. -J. Xie, W. Ni, Q. Wei, Z. -Y. Wu
Summary: A novel pathogenic PYCR2 variant was identified in two patients with spastic paraplegia, along with corresponding brain images.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Genetics & Heredity
Heba Morsy, Mehdi Benkirane, Elisa Cali, Clarissa Rocca, Kristina Zhelcheska, Valentina Cipriani, Evangelia Galanaki, Reza Maroofian, Stephanie Efthymiou, David Murphy, Mary O'Driscoll, Mohnish Suri, Siddharth Banka, Jill Clayton-Smith, Thomas Wright, Melody Redman, Jennifer A. Bassetti, Mathilde Nizon, Benjamin Cogne, Rami Abu Jamra, Tobias Bartolomaeus, Marion Heruth, Ilona Krey, Janina Gburek-Augustat, Dagmar Wieczorek, Felix Gattermann, Meriel Mcentagart, Alice Goldenberg, Lucie Guyant-Marechal, Hector Garcia-Moreno, Paola Giunti, Brigitte Chabrol, Severine Bacrot, Roger Buissonniere, Virginie Magry, Vykuntaraju K. Gowda, Varunvenkat M. Srinivasan, Bela Melegh, Andras Szabo, Katalin Sumegi, Mireille Cossee, Monica Ziff, Russell Butterfield, David Hunt, Georgina Bird-Lieberman, Michael Hanna, Michel Koenig, Michael Stankewich, Jana Vandrovcova, Henry Houlden
Summary: The purpose of this study was to understand the phenotypic spectrum of SPTAN1 variants. It was found that SPTAN1 variants were significantly enriched in families with hereditary ataxia or hereditary spastic paraplegia. A total of 31 individuals with SPTAN1 variants were identified, with 10 patients presenting with pure or complex HSP/HA and the remaining 21 patients having developmental delay and seizures. Fibroblasts derived from two patients showed irregular alpha II-spectrin aggregation.
GENETICS IN MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Asodu Sandeep Sarma, Bathula Siddardha, T. Pragna Lakshmi, Prajnya Ranganath, Ashwin Dalal
Summary: Exome sequencing analysis identified a novel homozygous synonymous variant in the SELENOI gene causing hereditary spastic paraplegia 81 in two affected siblings. This study expands the phenotypic and genotypic spectrum of hereditary spastic paraplegia 81.
JOURNAL OF GENE MEDICINE
(2023)
Article
Clinical Neurology
Marta Gatti, Stefania Magri, Daniela Di Bella, Elisa Sarto, Franco Taroni, Caterina Mariotti, Lorenzo Nanetti
Summary: SPG46 is a rare autosomal recessive hereditary spastic paraplegia caused by mutations in the GBA2 gene, leading to symptoms such as unsteady gait and spastic-ataxia. The disease presents with distinct clinical features and may overlap with other conditions.
NEUROLOGICAL SCIENCES
(2021)
Article
Oncology
Tao Shen, Wen Zhang, Li Li, Rong-Xia Zuo, Zi-Jun Wang, Tai Xiao, Kun-Wen Zheng
Summary: This study identified pathological candidate genes and variants in a large pedigree cohort of HSP patients in Yunnan Province using whole-exome sequencing. The SPAST gene was identified as a potential causative gene, while two other genes were found to have cumulative risks to the occurrence and progression of HSP. These findings provide useful diagnostic and therapeutic biomarkers for HSP.
ANNALS OF TRANSLATIONAL MEDICINE
(2022)
Article
Clinical Neurology
Ze-hua Lai, Xiao-ying Liu, Yuan-yue Song, Hai-yan Zhou, Li-li Zeng
Summary: Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by spasticity and weakness of the lower limbs. It has genetic and clinical heterogeneity, with four genetic inheritance forms. This study reports a new pathogenic variant in the ZFYVE26 gene, which is associated with HSP and presents with early cognitive impairment and slowly progressive leg weakness.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Haitian Nan, Min Chu, Li Liu, Kexin Xie, Liyong Wu
Summary: In this study, we identified a novel frameshift variant in the SPAST gene in a pure HSP family, suggesting haploinsufficiency as the pathogenic mechanism and expanding the known mutation spectrum of SPAST.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carolyn M. Kelly, Peter J. Zeiger, Vinodh Narayanan, Keri Ramsey, Holger Sondermann
Summary: Hereditary spastic paraplegia (HSP) is a group of neuropathies that affect upper motor neurons and cause progressive gait disorder. Mutations in the gene SPG3A/atlastin-1 (ATL1), which encodes a dynamin superfamily member involved in membrane tethering and fusion, account for approximately 10% of HSP cases. This study reports a novel disease-causing insertion mutation in the ATL1 gene, leading to severe quadriplegia, dystonia, and thinning of the corpus callosum. The mutation affects a region in the protein vital for intramolecular interactions and conformational changes driven by GTP hydrolysis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Clinical Neurology
Chao Zhang, Xiaowei Zhu, Zeyu Zhu, Ruilong Ni, Taotao Liu, Haoran Zheng, Shihua Liu, Li Cao, Ping Zhong, Wotu Tian
Summary: This study describes hereditary spastic paraplegia caused by a mutation in the UBAP1 gene, and provides a comprehensive review of the phenotypic features and genotype spectrum of this disease.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Jean-Madeleine de Sainte Agathe, Sandra Mercier, Jean-Yves Mahe, Yann Pereon, Julien Buratti, Laurene Tissier, Bophara Kol, Samia Ait Said, Eric Leguern, Guillaume Banneau, Giovanni Stevanin
Summary: The study confirms the involvement of biallelic truncating variants in the RNF170 gene in a novel form of hereditary spastic paraplegia, by analyzing a family with 4 affected members carrying a homozygous variant.
MOVEMENT DISORDERS
(2021)
Article
Pediatrics
Xin Xu, Fen Lu, Senjie Du, Xiaoke Zhao, Hongying Li, Li Zhang, Jian Tang
Summary: This article reports a very rare case of SPG54 caused by two novel compound heterozygous mutations in the DDHD2 gene. The mutations were confirmed to be deleterious through whole exome sequencing and multiple in silico prediction tools.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Hyun Mi Kang, Dae Hun Kim, Mijin Kim, Yoohong Min, Bohyeon Jeong, Kyung Hee Noh, Da Yong Lee, Hyun-Soo Cho, Nam-Soon Kim, Cho-Rok Jung, Jung Hwa Lim
Summary: This study discovered that the FBXL17-SPAST pathway is involved in the pathogenicity of hereditary spastic paraplegia (HSP) through loss of function and quantitative regulation. Targeting FBXL17 could provide new insights into HSP therapeutics.
CELL AND BIOSCIENCE
(2022)
Article
Neurosciences
Alonso Zea Vera, Ernest V. Pedapati, Travis R. Larsh, Kevin Kohmescher, Makoto Miyakoshi, David A. Huddleston, Hannah S. Jackson, Donald L. Gilbert, Paul S. Horn, Steve W. Wu
Summary: This study investigated the oscillatory changes in the right frontal lobe during motor inhibition in individuals with chronic tic disorders. The findings suggest that individuals with chronic tic disorders show greater event-related desynchronization in the right superior, middle, and inferior frontal gyral, which is associated with lower tic severity.
Article
Clinical Neurology
Gamze Kilic-Berkmen, Sarah Pirio Richardson, Joel S. Perlmutter, Mark Hallett, Christine Klein, Aparna Wagle-Shukla, Irene A. Malaty, Stephen G. Reich, Brian D. Berman, Jeanne Feuerstein, Marie Vidailhet, Emmanuel Roze, Joseph Jankovic, Abhimanyu Mahajan, Alberto J. Espay, Richard L. Barbano, Mark S. LeDoux, Alexander Pantelyat, Samuel Frank, Natividad Stover, Alfredo Berardelli, Julie Leegwater-Kim, Giovanni Defazio, Scott A. Norris, Hyder A. Jinnah
Summary: The study aimed to determine clinical features used by movement disorder specialists in the diagnosis and classification of isolated focal cervical dystonia, and to develop recommendations for a more consistent approach to classification. Results showed that even though diagnosed with isolated focal cervical dystonia, a high percentage of subjects exhibited dystonia outside of the neck region, indicating the need for more specific guidelines for defining this common disorder.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2022)
Article
Clinical Neurology
Cullen S. Marshall, Stella Deng, Hannah S. Jackson, Paul S. Horn, David S. Wolf, Robert Thompson-Stone, Donald L. Gilbert
Summary: This study aimed to investigate the implementation of revised adult neurology training requirements by child neurology and neurodevelopmental disabilities residency program directors in the United States. Most programs still concentrate adult training in the PGY-3 year and often schedule additional hospital shifts during outpatient and elective months. Few programs require rotations in adult neurophysiology, neuropathology, or neuroradiology.
Article
Neurosciences
Travis R. Larsh, David A. Huddleston, Paul S. Horn, Steve W. Wu, Kim M. Cecil, Hannah S. Jackson, Richard A. E. Edden, Stewart H. Mostofsky, Donald L. Gilbert
Summary: Tourette syndrome (TS) is a childhood-onset disorder characterized by tics preceded by premonitory sensory urges. This study found that the intensity of the urges strongly correlated with tic severity. More severe urges were associated with lower cortical excitability (CE) and weaker cortical inhibition in both right and left M1. Interestingly, in the right M1, lower CE and weaker inhibition correlated with less severe tics. The study suggests that in young children with TS, the reduction of CE and inhibition in the right M1, modulated by the supplementary motor area (SMA) and gamma-amino butyric acid (GABA), may serve as compensatory mechanisms to diminish tics in response to premonitory urges.
Article
Neurosciences
Roderick T. Hori, Mohammad Moshahid Khan, Jianfeng Xiao, Phillip W. Hargrove, Tom Moss, Mark S. LeDoux
Summary: The UBTF E210K neuroregression syndrome is caused by mutations in the UBTF gene, leading to negative effects on neural function in humans. Through mouse experiments, it was discovered that reduced or silenced Ubtf gene resulted in abnormal behavior, cognition, motor skills, and molecular level changes, suggesting that loss-of-function mechanisms may play a role in humans as well.
Article
Clinical Neurology
Davide Martino, Tammy Hedderly, Tara Murphy, Kirsten R. Mueller-Vahl, Russell C. Dale, Donald L. Gilbert, Renata Rizzo, Andreas Hartmann, Peter Nagy, Mathieu Anheim, Tamsin Owen, Osman Malik, Morvwen Duncan, Isobel Heyman, Holan Liang, Andrew McWilliams, Shauna O'Dwyer, Carolin Fremer, Natalia Szejko, Velda X. Han, Kasia Kozlowska, Tamara M. Pringsheim
Summary: There has been a significant increase in adolescents and young adults seeking urgent help for functional tic-like behaviors (FTLBs) between 2019 and 2022. An international collaborative group collected retrospective data to better understand this spectrum and its clinical differences from primary tic disorders. The study findings suggest that social media exposure may be a relevant contributing factor to FTLBs.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Alonso Zea Vera, Adrienne Bruce, Travis R. Larsh, Zachary Jordan, Norbert Bruggemann, Ana Westenberger, Alberto J. Espay, Donald L. Gilbert, Steve W. Wu
Summary: POLR3A-related disorders exhibit significant phenotypic pleomorphism, including a range of movement disorders such as parkinsonism, dystonia, ataxia, and spasticity. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Mitchell A. Batschelett, David A. Huddleston, Deana Crocetti, Paul S. Horn, Stewart H. Mostofsky, Donald L. Gilbert
Summary: This study compared transcranial magnetic stimulation (TMS)-derived measures of primary motor cortex (M1) physiology between children with and without Tourette syndrome, and found that reduced M1 short-interval cortical inhibition (SICI) is associated with increased tic severity, but not urge severity.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Clinical Neurology
Travis R. Larsh, Steve W. W. Wu, David A. Huddleston, Sean White, Tara D. Lipps, Donald L. Gilbert
Summary: This study aimed to compare tic- and non-tic-related impairment experienced by adolescent boys and girls with Tourette syndrome, and its association with age. Data from electronic health records and questionnaires were analyzed for 132 unique adolescent encounters. The findings suggest that tic- and non-tic-related impairment may improve with age in boys but not in girls, and that obsessive-compulsive symptoms are associated with non-tic-related impairment in girls. Further longitudinal studies are needed to confirm these findings.
JOURNAL OF CHILD NEUROLOGY
(2023)
Article
Clinical Neurology
Travis R. Larsh, Steve W. Wu, David A. Huddleston, Tara D. Lipps, Donald L. Gilbert
Summary: This study aimed to compare sex differences in tic severity among adolescents with Tourette syndrome (TS) before and during the COVID-19 pandemic. The study found that during the pandemic, boys had less severe tics compared to girls, while there were no significant differences in tic severity between boys and girls before the pandemic.
Article
Genetics & Heredity
Karen M. Bailey, Navdeep Sahota, Uyen To, Peter Hedera
Summary: This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of Wilson disease (WD) in the US. Through interviews with 12 patients and 7 specialist physicians, the study found issues in diagnosis journey, multidisciplinary approach, medication, the role of insurance, and education, awareness, and support. The study emphasizes the importance of easy access to reliable and up-to-date information for physicians, patients, and their caregivers, as well as general community outreach programs.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Clinical Neurology
Alexander C. Doherty, David A. Huddleston, Paul S. Horn, Nancy Ratner, Brittany N. Simpson, Elizabeth K. Schorry, Lindsey Aschbacher-Smith, Carlos E. Prada, Donald L. Gilbert
Summary: Neurofibromatosis type 1 (NF1) is a genetic disorder with motor and cognitive symptoms that severely impact quality of life. This study used transcranial magnetic stimulation (TMS) to assess motor cortex physiology in children with NF1, ADHD, and typically developing (TD) children. It was found that children with NF1 had impaired motor function and altered motor cortex physiology compared to TD and ADHD children.
PEDIATRIC NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Marc P. Forrest, Marc Dos Santos, Nicolas H. Piguel, Yi-Zhi Wang, Nicole A. Hawkins, Vikram A. Bagchi, Leonardo E. Dionisio, Sehyoun Yoon, Dina Simkin, Maria Dolores Martin-de-Saavedra, Ruoqi Gao, Katherine E. Horan, Alfred L. George Jr, Mark S. LeDoux, Jennifer A. Kearney, Jeffrey N. Savas, Peter Penzes
Summary: This study reveals that the 16p11.2 duplication increases the risk of autism and schizophrenia, and proteomics analysis shows that it causes dysregulation of synaptic and epilepsy-associated protein networks. The authors also demonstrate that correcting Prrt2 gene dosage can rescue circuit hypersynchrony and behavioral phenotypes. These findings contribute to our understanding of the biological basis of neuropsychiatric disorders and epilepsy.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Erin Furr Stimming, Daniel Claassen, Elise Kayson, Jody Goldstein, Raja Mehanna, Hui Zhang, Grace S. Liang, Dietrich Haubenberger
Summary: Valbenazine was evaluated as a treatment for chorea associated with Huntington's disease, and it was found to be more effective than placebo in improving chorea symptoms and well tolerated.
Article
Medicine, General & Internal
Muhammad Ismail Khalid Yousaf, Mohammad Ravi Ghani, Talita D'Aguiar Rosa, Victoria Holiday, Martin Brown, Peter Hedera
Summary: Myokymia is a condition characterized by hyperexcitability of muscle fibers due to repetitive spontaneous contractions of motor units. This study reports two cases of continuous myokymia, which were effectively treated with botulinum toxin.
SAGE OPEN MEDICAL CASE REPORTS
(2022)