Article
Clinical Neurology
Claudia Dosi, Rosa Pasquariello, Chiara Ticci, Guja Astrea, Rosanna Trovato, Anna Rubegni, Alessandra Tessa, Giovanni Cioni, Filippo Maria Santorelli, Roberta Battini
Summary: HSPs are a genetically and clinically diverse group of neurodegenerative disorders characterized by progressive spasticity of the lower limbs. MRI can help in excluding mimicking disorders and guiding genetic testing.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Review
Clinical Neurology
Simone Aloisio, Sara Satolli, Gabriele Bellini, Piervito Lopriore
Summary: Parkinsonism is a syndrome characterized by bradykinesia accompanied by rest tremor, rigidity, or both. It is commonly seen in Parkinson's disease and atypical parkinsonian disorders. However, it can also be a manifestation of complex neurogenetic diseases. Understanding the clinical features of parkinsonism in adult-onset neurogenetic diseases is important for understanding pathophysiological mechanisms and for clinical diagnosis and treatment.
NEUROLOGICAL SCIENCES
(2023)
Review
Pathology
Grainne Mulkerrin, Marcondes C. Franca, Jasmin Lope, Ee Ling Tan, Peter Bede
Summary: This article reviews the progress of imaging techniques in hereditary spastic paraplegias (HSP). The study highlights the use of various imaging modalities, study design, clinical correlations, and methodological approaches in HSP cohorts. Current limitations include genetically admixed cohorts, small sample sizes, lack of postmortem validation, and limited clinical battery. However, collaborative multicenter initiatives and comprehensive clinical profiling have the potential to overcome these limitations and develop viable clinical applications for HSP imaging.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2022)
Article
Neurosciences
Diana Maria Cubillos-Arcila, Gustavo Dariva Machado, Lauren Sehnem, Daniela Burguez, Ana Paula Janner Zanardi, Valeria Feijo Martins, Leonardo Alexandre Peyre-Tartaruga, Jonas Alex Morales Saute
Summary: The study found that functional gait performance in individuals with HSP was significantly impaired compared to controls, but after 18 months of follow-up, there was no significant difference in TFT performance from baseline, with some tests showing more frequent improvement. TFTs were effective instruments for assessing disease severity, but did not fully capture the very slow motor evolution of HSPs, highlighting the need for additional biomarkers of disease progression.
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
Multidisciplinary Sciences
Gabriela Marchisio Giordani, Fabricio Diniz, Helena Fussiger, Carelis Gonzalez-Salazar, Karina Carvalho Donis, Fernando Freua, Roberta Paiva Magalhaes Ortega, Julian Leticia de Freitas, Orlando Graziani Povoas Barsottini, Sergio Rosemberg, Fernando Kok, Jose Luiz Pedroso, Marcondes Cavalcante Franca Jr, Jonas Alex Morales Saute
Summary: The study characterized clinical and molecular data of a large cohort with childhood-onset hereditary spastic paraplegias, identifying SPG4 and SPG3A as the most common childhood-onset subtypes. Most childhood-onset HSP cases had missense pathogenic variants in SPAST, leading to slow neurological deterioration, with a variety of complicating features reported.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Diana Maria Cubillos Arcila, Gustavo Dariva Machado, Valeria Feijo Martins, Vanessa Bielefeldt Leotti, Rebecca Schuele, Leonardo Alexandre Peyre-Tartaruga, Jonas Alex Morales Saute
Summary: The study found that both performance and clinician-reported outcomes can capture long-term progression of HSPs, with some gait performance outcomes showing greater sensitivity to change. The data presented are crucial for planning future therapeutic trials for this currently untreatable group of diseases.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Hiromi Fukuda, Takeshi Mizuguchi, Hiroshi Doi, Shinichi Kameyama, Misako Kunii, Hideto Joki, Tatsuya Takahashi, Hiroyasu Komiya, Mei Sasaki, Yosuke Miyaji, Sachiko Ohori, Eriko Koshimizu, Yuri Uchiyama, Naomi Tsuchida, Atsushi Fujita, Kohei Hamanaka, Kazuharu Misawa, Satoko Miyatake, Fumiaki Tanaka, Naomichi Matsumoto
Summary: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower extremities. Exome sequencing (ES) is commonly used for diagnosis, but long-read sequencing is more efficient in detecting intragenic deletions in HSP patients that are ES-negative.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Peiqiang Li, Xiande Huang, Senmao Chai, Dalin Zhu, Huirong Huang, Fengdie Ma, Shasha Zhang, Xiaodong Xie
Summary: This article reports a Chinese family with HSP caused by a mutation in the UBAP1 gene. The study finds that UBAP1-related HSP patients have early onset and commonly experience lower extremity spasticity, hyperreflexia, and the Babinski sign.
FRONTIERS IN GENETICS
(2022)
Article
Neurosciences
Yongping Chen, Gopinath Krishnan, Sepideh Parsi, Marine Pons, Veroniki Nikolaki, Lu Cao, Zuoshang Xu, Fen-Biao Gao
Summary: The enhanced association between mutant CHMP2B and spastin may represent a novel pathological link between FTD3 and HSP. This association could contribute to the development of FTD3 and HSP.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Claudia Schob, Maja Hempel, Dana Safka Brozkova, Huafang Jiang, Soo Yeon Kim, Nurit Assia Batzir, Naama Orenstein, Tatjana Bierhals, Jessika Johannsen, Anna Uhrova Meszarosova, Jong-Hee Chae, Pavel Seeman, Mathias Woidy, Fang Fang, Christian Kubisch, Stefan Kindler, Jonas Denecke
Summary: The study identified heterozygous variants in KPNA3 as the genetic basis for pure infantile-onset hereditary spastic paraplegia. Mutant karyopherin-alpha 3 proteins exhibit varying deficits in molecular and cellular functions.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Manuela Wiessner, Reza Maroofian, Meng-Yuan Ni, Andrea Pedroni, Juliane S. Muller, Rolf Stucka, Christian Beetz, Stephanie Efthymiou, Filippo M. Santorelli, Ahmed A. Alfares, Changlian Zhu, Anna Uhrova Meszarosova, Elham Alehabib, Somayeh Bakhtiari, Andreas R. Janecke, Maria Gabriela Otero, Jin Yun Helen Chen, James T. Peterson, Tim M. Strom, Peter De Jonghe, Tine Deconinck, Willem De Ridder, Jonathan De Winter, Rossella Pasquariello, Ivana Ricca, Majid Alfadhel, Bart P. van de Warrenburg, Ruben Portier, Carsten Bergmann, Saghar Ghasemi Firouzabadi, Sheng Chih Jin, Kaya Bilguvar, Sherifa Hamed, Mohammed Abdelhameed, Nourelhoda A. Haridy, Shazia Maqbool, Fatima Rahman, Najwa Anwar, Jenny Carmichael, Alistair Pagnamenta, Nick W. Wood, Frederic Tran Mau-Them, Tobias Haack, Maja Di Rocco, Isabella Ceccherini, Michele Iacomino, Federico Zara, Vincenzo Salpietro, Marcello Scala, Marta Rusmini, Yiran Xu, Yinghong Wang, Yasuhiro Suzuki, Kishin Koh, Haitian Nan, Hiroyuki Ishiura, Shoji Tsuji, Laetitia Lambert, Emmanuelle Schmitt, Elodie Lacaze, Hanna Kuepper, David Dredge, Cara Skraban, Amy Goldstein, Mary J. H. Willis, Katheryn Grand, John M. Graham, Richard A. Lewis, Francisca Millan, Ozgur Duman, Nihal Dundar, Gokhan Uyanik, Ludger Schols, Peter Nuernberg, Gudrun Nuernberg, Andrea Catala Bordes, Pavel Seeman, Martin Kuchar, Hossein Darvish, Adriana Rebelo, Filipa Boucanova, Jean-Jacques Medard, Roman Chrast, Michaela Auer-Grumbach, Fowzan S. Alkuraya, Hanan Shamseldin, Saeed Al Tala, Jamileh Rezazadeh Varaghchi, Maryam Najafi, Selina Deschner, Dieter Glaeser, Wolfgang Huettel, Michael C. Kruer, Erik-Jan Kamsteeg, Yoshihisa Takiyama, Stephan Zuchner, Jonathan Baets, Matthis Synofzik, Rebecca Schuele, Rita Horvath, Henry Houlden, Luca Bartesaghi, Hwei-Jen Lee, Konstantinos Ampatzis, Tyler Mark Pierson, Jan Senderek
Summary: This study identified families with neurological diseases caused by HPDL variants, showing various phenotypes ranging from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia. Experimental evidence suggested a role of HPDL in the nervous system and supported its link to neurological disease.
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.
Review
Biochemical Research Methods
Chiara Martinello, Emanuele Panza, Antonio Orlacchio
Summary: Investigating the shared pathogenetic mechanisms underlying different subtypes of HSP is crucial for understanding the disease and developing effective treatments. By examining disease-causing gene products and their associated functional pathways, new therapeutic targets can be identified, leading to potential advancements in HSP diagnosis and treatment.
EXPERT REVIEW OF PROTEOMICS
(2023)
Article
Genetics & Heredity
Akgun Olmez, Gokhan Ozan Cetin, Kadri Karaer
Summary: Hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive gait impairment and lower extremity spasticity. There are more than 80 defined types of HSP. Genetic testing and imaging results are crucial for diagnosis.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Letter
Clinical Neurology
Haitian Nan, Ryusuke Takaki, Yuta Ichinose, Mai Tsuchiya, Kishin Koh, Shuji Hanyu, Kazumasa Shindo, Yoshihisa Takiyama
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2018)
Article
Genetics & Heredity
Kishin Koh, Yuta Ichinose, Hiroyuki Ishiura, Haitian Nan, Jun Mitsui, Junya Takahashi, Wakiro Sato, Yoshiaki Itoh, Kyoko Hoshino, Shoji Tsuji, Yoshihisa Takiyama
JOURNAL OF HUMAN GENETICS
(2019)
Article
Clinical Neurology
Haitian Nan, Ryusuke Takaki, Takanori Hata, Yuta Ichinose, Mai Tsuchiya, Kishin Koh, Yoshihisa Takiyama
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2019)
Article
Medicine, General & Internal
Haitian Nan, Keisuke Shimozono, Yuta Ichinose, Mai Tsuchiya, Kishin Koh, Masaki Hiraide, Yoshihisa Takiyama
Article
Clinical Neurology
Takanori Hata, Takamura Nagasaka, Kishin Koh, Mai Tsuchiya, Yuta Ichinose, Haitian Nan, Kazumasa Shindo, Yoshihisa Takiyama
Article
Medicine, General & Internal
Haitian Nan, Ryusuke Takaki, Keisuke Shimozono, Yuta Ichinose, Kishin Koh, Yoshihisa Takiyama
Letter
Clinical Neurology
Haitian Nan, Takahiro Natori, Yuta Ichinose, Kishin Koh, Fumikazu Kobayashi, Kazumasa Shindo, Masaki Hashiyada, Noboru Adachi, Zentaro Yamagata, Yoshihisa Takiyama
PARKINSONISM & RELATED DISORDERS
(2019)