Article
Clinical Neurology
Ruizhi Deng, Eva Medico-Salsench, Anita Nikoncuk, Reshmi Ramakrishnan, Kristina Lanko, Nikolas A. Kuhn, Herma C. van der Linde, Sarah Lor-Zade, Fatimah Albuainain, Yuwei Shi, Soheil Yousefi, Ivan Capo, Evita Medici van den Herik, Marjon van Slegtenhorst, Rick van Minkelen, Geert Geeven, Monique T. Mulder, George J. G. Ruijter, Dieter Luetjohann, Edwin H. Jacobs, Henry Houlden, Alistair T. Pagnamenta, Kay Metcalfe, Adam Jackson, Siddharth Banka, Lenika De Simone, Abigail Schwaede, Nancy Kuntz, Timothy Blake Palculict, Safdar Abbas, Muhammad Umair, Mohammed AlMuhaizea, Dilek Colak, Hanan AlQudairy, Maysoon Alsagob, Catarina Pereira, Roberta Trunzo, Vasiliki Karageorgou, Aida M. Bertoli-Avella, Peter Bauer, Arjan Bouman, Lies H. Hoefsloot, Tjakko J. van Ham, Mahmoud Issa, Maha S. Zaki, Joseph G. Gleeson, Rob Willemsen, Namik Kaya, Stefan T. Arold, Reza Maroofian, Leslie E. Sanderson, Tahsin Stefan Barakat
Summary: Hereditary spastic paraplegias (HSP) are rare inherited disorders characterized by lower limb spasticity and muscle weakness. Researchers identified bi-allelic truncating variants in the AMFR gene in HSP-affected individuals, leading to a better understanding of the disease. The absence of AMFR disrupts lipid homeostasis and affects ER morphology, but treatment with statins shows potential therapeutic implications.
ACTA NEUROPATHOLOGICA
(2023)
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
Genetics & Heredity
Valeriia A. Kovalskaia, Victoriia V. Zabnenkova, Marina S. Petukhova, Zhanna G. Markova, Vyacheslav Yu. Tabakov, Oxana P. Ryzhkova
Summary: Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a rare genetic disease caused by biallelic pathogenic variants in the HACE1 gene. We report a clinical case of a 2-year-old male with previously undescribed HACE1 biallelic deletions as the causative gene. Comprehensive diagnostic approaches are needed for patients initially diagnosed with homozygous mutations in HACE1 to overcome false homozygosity.
Article
Clinical Neurology
Yi-Jun Chen, Zai-Qiang Zhang, Meng-Wen Wang, Yu-Sen Qiu, Ru-Ying Yuan, En-Lin Dong, Zhe Zhao, Hai-Tao Zhou, Ning Wang, Wan-Jin Chen, Xiang Lin
Summary: This study identified a novel ALDH18A1 gene mutation and demonstrated the value of splicing mutation prediction in characterizing disease-related intronic variants. The detected variant led to significantly decreased P5CS concentration in the proband's plasma compared to healthy controls. Furthermore, review of previously reported recessive cases indicated that SPG9B patients in this cohort presented with milder symptoms.
FRONTIERS IN NEUROLOGY
(2021)
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
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
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)
Review
Behavioral Sciences
Shuai Chen, Jin-Long Zou, Shuang He, Wei Li, Jie-Wen Zhang, Shu-Jian Li
Summary: This study reported the first autosomal dominant SPG18 pedigree in the Chinese Han population, providing additional evidence for the pathogenicity of the V168M mutation. Clinical phenotype of AD-SPG18 is characterized by juvenile-adolescent onset pure HSP, while AR-SPG18 is mostly characterized by complicated HSP with earlier onset and more severe conditions.
BRAIN AND BEHAVIOR
(2021)
Article
Biotechnology & Applied Microbiology
Jin Ok Yang, Ji-Yong Yoon, Duk Hyun Sung, Sohyun Yun, Jeong-Ju Lee, Soo Young Jun, Debasish Halder, Su-Jin Jeon, Eui-Jeon Woo, Jin Myoung Seok, Jin Whan Cho, Ja-Hyun Jang, Jung Kyoon Choi, Byoung Joon Kim, Nam-Soon Kim
Summary: This study identified 88 genetic variants in 54 genes from whole-exome data of 82 clinically well-defined Korean HSP families, expanding the genetic spectrum for HSP and potentially contributing to more accurate diagnosis and treatment for rare HSP. The inheritance modes varied, with 39 de novo, 33 autosomal dominant, and 10 autosomal recessive cases. Furthermore, the study revealed differences in the genetic spectrum and variation of known HSP genes across ethnic groups.
Article
Biochemistry & Molecular Biology
Ece Selcuk, Koray Kirimtay, Benan Temizci, Seyma Akarsu, Elif Everest, Mehmet Baris Baslo, Meltem Demirkiran, Zuhal Yapici, Arzu Karabay
Summary: In this study, the genetic basis of a Turkish family with hereditary spastic paraplegia (HSP) was determined using exome sequencing. A variant in the MYO1H gene was identified as a possible disease-causing deletion for HSP in this family.
MOLECULAR GENETICS AND GENOMICS
(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
Behavioral Sciences
Ji-Qing Duan, Hui Liu, Jia-Qiao Wu
Summary: A 24-year-old man with progressive gait disturbance was diagnosed with autosomal recessive hereditary spastic paraplegia. Whole genome sequencing identified two novel mutations (c.5687_5691del and c.751C>T) in the SPG11 gene of the patient. The frameshift mutation (c.5687_5691del) caused a change in amino acid synthesis, resulting in premature termination of peptide synthesis due to the non-sense mutation (c.751C>T). Although compound-heterozygosity confirmation was not performed, our findings expand the phenotypic spectrum of SPG11 mutations associated with hereditary spastic paraplegia.
FRONTIERS IN INTEGRATIVE NEUROSCIENCE
(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
Yi-Jun Chen, Meng-Wen Wang, Yu-Sen Qiu, Ru-Ying Yuan, Ning Wang, Xiang Lin, Wan-Jin Chen
Summary: The molecular cause of hereditary spastic paraplegia (HSP) in a four-generation family with autosomal dominant inheritance was diagnosed using MLPA, WES, and RNA-seq. An intronic AluYb9 insertion in the edge of intron 16 in SPAST was identified, which segregated with the disease phenotype. Our findings suggest that RNA-seq is a recommended first-line diagnostic approach for undiagnosed cases.
MOVEMENT DISORDERS
(2023)
