Article
Cell Biology
Saurabh Srivastav, Kevin van der Graaf, Pratibha Singh, Alloysius Budi Utama, Matthew D. Meyer, James A. Mcnew, Michael Stern
Summary: This study using a Drosophila model found that the absence of atlastin protein leads to muscle issues and affects the autophagy pathway and MTOR signaling. Therefore, the research suggests that mutations in the ATL1/SPG3A gene may cause pathological changes in patients with HSP.
Letter
Clinical Neurology
Rithvik Ramesh, Anu Deenadayalu, Shakya Bhattacharjee, Vijayashankar Paramanandam
Summary: Mitochondrial Membrane-protein Associated Neurodegeneration (MPAN) is a rare disease caused by C19orf12 mutations, with up to 29 different mutations described. We report a case of a young woman presenting with spastic paraparesis due to a C19orf12 gene mutation, which has been described only once in the literature and presents similarly to Hereditary spastic paraplegia-43.
PARKINSONISM & RELATED DISORDERS
(2021)
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)
Review
Biochemistry & Molecular Biology
Arun Meyyazhagan, Antonio Orlacchio
Summary: This review provides an overview of hereditary spastic paraplegia (HSP), including its clinical manifestations, etiology, diagnosis, and treatment methods. Although modern medical interventions have helped, there is still room for improvement in the treatment of this disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Julian Emanuel Alecu, Yuhsuke Ohmi, Robiul H. Bhuiyan, Kei-ichiro Inamori, Takahiro Nitta, Afshin Saffari, Hellen Jumo, Marvin Ziegler, Claudio Melo de Gusmao, Nutan Sharma, Shiho Ohno, Noriyoshi Manabe, Yoshiki Yamaguchi, Mariko Kambe, Keiko Furukawa, Mustafa Sahin, Jin-ichi Inokuchi, Koichi Furakawa, Darius Ebrahimi-Fakhari
Summary: This article presents a case study of a 13-year-old female patient with childhood-onset hereditary spastic paraplegia. The patient exhibited developmental delay, intellectual disability, and various motor and neurological symptoms. Through functional studies and genetic sequencing, a new variant in the B4GALNT1 gene was identified as the cause of the disease. The study highlights the importance of careful phenotyping and functional characterization of novel gene variants in rare diseases.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Clinical Neurology
Afshin Saffari, Melanie Kellner, Catherine Jordan, Helena Rosengarten, Alisa Mo, Bo Zhang, Oleksandr Strelko, Sonja Neuser, Marie Y. Davis, Nobuaki Yoshikura, Naonobu Futamura, Tomoya Takeuchi, Shin Nabatame, Hiroyuki Ishiura, Shoji Tsuji, Huda Shujaa Aldeen, Elisa Cali, Clarissa Rocca, Henry Houlden, Stephanie Efthymiou, Birgit Assmann, Grace Yoon, Bianca A. Trombetta, Pia Kivisakk, Florian Eichler, Haitian Nan, Yoshihisa Takiyama, Alessandra Tessa, Filippo M. Santorelli, Mustafa Sahin, Craig Blackstone, Edward Yang, Rebecca Schuele, Darius Ebrahimi-Fakhari
Summary: This study delineates the clinical, neuroimaging, and molecular features of ZFYVE26-associated hereditary spastic paraplegia (HSP-ZFYVE26) patients. Most patients present with motor and/or speech delay, progressive spasticity, and extrapyramidal movement disorders. Elevated plasma neurofilament light chain levels correlate with disease severity.
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)
Review
Neurosciences
Emanuele Panza, Arun Meyyazhagan, Antonio Orlacchio
Summary: Hereditary Spastic Paraplegias (HSPs) are a group of heterogeneous diseases characterized by progressive spasticity and weakness of the lower limbs. Although HSPs are rare conditions, they pose significant health and economic challenges. The molecular diagnostic rate for HSPs is variable, suggesting the involvement of more genes and the need for different diagnostic approaches. HSPs exhibit genetic heterogeneity, allelic heterogeneity, and overlap with other neurological conditions.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Qiao Wei, Hao Yu, Pei-Shan Wang, Juan-Juan Xie, Hai-Lin Dong, Zhi-Ying Wu, Hong-Fu Li
Summary: This study identified five different COQ4 variants in three Chinese HSP pedigrees, expanding the phenotypic spectrum of COQ4-related disorders. Additionally, two early-onset pure HSP cases caused by COQ4 variants were described for the first time.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Neurosciences
Wenchao Xiong, Liqiang Jin, Yulu Zhao, Yu Wu, Jinghua Dong, Zhixin Guo, Minzhen Zhu, Yongfeng Dai, Yida Pan, Xinhong Zhu
Summary: Hereditary spastic paraplegia (HSP) is a severe neurodegenerative movement disorder. Dysregulation of iron homeostasis may be involved in the pathophysiology of HSP. Studying PV+ interneurons, researchers found that the deletion of transferrin receptor 1 (TFR1) in these neurons led to motor deficits and other pathological features, which could be rescued by iron repletion.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
Francesca Sardina, Davide Valente, Gaia Fattorini, Ettore Cioffi, Gianmarco Dalla Zanna, Alessandra Tessa, Daniela Trisciuoglio, Silvia Soddu, Filippo M. Santorelli, Carlo Casali, Cinzia Rinaldo
Summary: The study developed an automated, simple, fast, and non-invasive cell imaging-based method to quantify microtubule cytoskeleton organization changes in lymphoblastoid cells and peripheral blood mononuclear cells. The results showed that individuals affected by SPG4-hereditary spastic paraplegia have a polarized microtubule cytoskeleton organization. The method was able to discriminate SPG4-hereditary spastic paraplegia from healthy donors and other subtypes, and detect the effects of spastin protein level changes.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D. Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K. G. Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C. Spillmann, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J. Bellen, Simon Edvardson, Florian Eichler, Teresa M. Dunn
Summary: Sphingolipids, abundant in myelin membranes, are crucial for the structural and signalling functions in the mammalian nervous system. Serine palmitoyltransferase (SPTSSA) is the enzyme responsible for the rate-limiting reaction in sphingolipid synthesis and its activity is tightly regulated by ORMDL proteins. Excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase was found to be responsible for defects in early brain development and function. SRivastava et al. identified SPTSSA variants that disrupt ORMDL-mediated regulation of SPT, leading to hereditary spastic paraplegia.
Article
Clinical Neurology
Azusa Ikeda, Tatsuro Kumaki, Yu Tsuyusaki, Megumi Tsuji, Yumi Enomoto, Atsushi Fujita, Hirotomo Saitsu, Naomichi Matsumoto, Kenji Kurosawa, Tomohide Goto
Summary: This study retrospectively evaluated the genetic analyses, family history, clinical courses, MRI findings, and electrophysiologic findings of children diagnosed with pediatric-onset hereditary spastic paraplegias (HSPs) at a tertiary pediatric hospital in Japan. The causative gene patterns differed between children with pure-type and complex-type HSPs.
FRONTIERS IN NEUROLOGY
(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)
Review
Neurosciences
Jose Luiz Pedroso, Thiago Cardoso Vale, Marcondes C. Franca Junior, Marcelo A. Kauffman, Helio Teive, Orlando Graziani Povoas Barsottini, Renato Puppi Munhoz
Summary: Spastic ataxia is characterized by the combination of cerebellar ataxia with spasticity and other pyramidal features. This condition can present with heterogeneous clinical features along with other neurologic and non-neurological symptoms, resulting in complex phenotypes. Establishing an organized classification method based on mode of inheritance is essential for approaching patients with these syndromes, and a diagnostic approach is proposed in this review.
Article
Medicine, Research & Experimental
Qi-Jie Zhang, Xiang Lin, Jin-Jing Li, Ying-Qian Lu, Xin-Xin Guo, Miao Zhao, Jin He, Ning Wang, Wan-Jin Chen
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2017)
Article
Oncology
Xiang Lin, Jin-Jing Li, Wen-Jing Qian, Qi-Jie Zhang, Zhong-Feng Wang, Ying-Qian Lu, En-Lin Dong, Jin He, Ning Wang, Li-Xiang Ma, Wan-Jin Chen
Article
Clinical Neurology
Xiang Lin, Qi-Jie Zhang, Jin He, Min-Ting Lin, Shen-Xing Murong, Ning Wang, Wan-Jin Chen
JOURNAL OF CHILD NEUROLOGY
(2014)
Article
Cell & Tissue Engineering
Ying-qian Lu, En-lin Dong, Wei-qi Yang, Lu-lu Lai, Xiao-hong Lin, Li-xiang Ma, Wan-jin Chen, Ning Wang, Xiang Lin
STEM CELL RESEARCH
(2019)
Article
Clinical Neurology
Yi-Jun Chen, Meng-Wen Wang, En-Lin Dong, Xiao-Hong Lin, Ning Wang, Zai-Qiang Zhang, Xiang Lin, Wan-Jin Chen
PARKINSONISM & RELATED DISORDERS
(2019)
Article
Genetics & Heredity
Miao Zhao, Yi-Jun Chen, Meng-Wen Wang, Xiao-Hong Lin, En-Lin Dong, Wan-Jin Chen, Ning Wang, Xiang Lin
MOLECULAR DIAGNOSIS & THERAPY
(2019)
Article
Clinical Neurology
Lu-Lu Lai, Yi-Jun Chen, Yun-Lu Li, Xiao-Hong Lin, Meng-Wen Wang, En-Lin Dong, Ning Wang, Wan-Jin Chen, Xiang Lin
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2020)