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)
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)
Letter
Clinical Neurology
Rui Ban, Chuanqiang Pu, Fang Fang, Qiang Shi
Summary: SPG78 is a subtype of hereditary spastic paraplegia caused by ATP13A2 gene mutations. While it has been reported as complicated HSP in some cases, it has never been associated with pure HSP. The first Chinese patient carrying a novel homozygous nonsense mutation in ATP13A2 presenting with pure HSP was reported in this study.
PARKINSONISM & RELATED DISORDERS
(2021)
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
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
Shao-Lun Hsu, Hsueh-Wen Hsueh, Shih-Ying Chen, Yung-Yee Chang, Shennie Tan, Chien-Tai Hong, Yu-Shuen Tsai, Kai-Wei Yu, Hsiu-Mei Wu, Yi-Chu Liao, Bing-Wen Soong, Chaur-Jong Hu, Min-Yu Lan, Yi-Chung Lee
Summary: This study investigated the clinical and genetic features of SPG3A in Taiwan and identified that SPG3A accounts for 4% of HSP cases in Taiwan. The most common mutation found in SPG3A patients was ATL1 p.R416C, with 18 patients typically presenting with a pure form HSP phenotype. Haplotype analysis suggested a shared haplotype in patients carrying the p.R416C allele.
PARKINSONISM & RELATED DISORDERS
(2021)
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
Oncology
Xing-Chen Wang, Rui-Han Liu, Ting Wang, Yanling Wang, Yan Jiang, Dan-Dan Chen, Xin-Yu Wang, Tong-Shu Hou, Qing-Xia Kong
Summary: This study reports a mutation causing SPG4 and describes the clinical characteristics of affected family members. All affected individuals in the family exhibited lower limb spasticity and weakness, and only males were affected. Whole-exome sequencing revealed a novel c.1785C>A (p. Ser595Arg) missense mutation in the SPAST gene in all affected individuals. Bioinformatics analysis showed changes in the secondary and tertiary structures of the mutated protein. This novel missense mutation in SPAST supports the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations causing SPG4.
MOLECULAR MEDICINE REPORTS
(2023)
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
Noriko Miyake, Sebastian Silva, Monica Troncoso, Nobuhiko Okamoto, Yoshiki Andachi, Mitsuhiro Kato, Chisato Iwabuchi, Mio Hirose, Atsushi Fujita, Yuri Uchiyama, Naomichi Matsumoto
Summary: ABHD16A-related HSP is a genetically and clinically heterogeneous disease characterized by early onset in childhood, developmental delay, intellectual disability, and other symptoms. Affected individuals may also exhibit characteristic facial features, sleep disturbances, and skin lesions.
Article
Medical Laboratory Technology
Zhaoyu Wang, Huijie Dong, Xiaofei Ji, Siyu Luan, Hua Cao
Summary: This study reported a rare insertion mutation site in PRRT2 causing familial hereditary spastic paraplegia with polyneuropathy. The discovery of this mutation site provides an important theoretical basis for specific gene-based diagnosis and treatment of hereditary spastic paraplegia.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
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
Genetics & Heredity
Jun Fu, Mingming Ma, Gang Li, Jiewen Zhang
Summary: This study identified two variants of the NIPA1 gene in three Chinese families with HSP. The NIPA1-related HSP was found to be more common in China than in Europe, with both pure and complicated forms of the disease. One variant was a common mutation, while the other was a novel likely pathogenic variant.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Ethiraj Ravindran, Cynthia Gutierrez de Velazco, Ali Ghazanfar, Nadine Kraemer, Sami Zaqout, Abdul Waheed, Mohsan Hanif, Sadia Mughal, Alessandro Prigione, Na Li, Xiang Fang, Hao Hu, Angela M. Kaindl
Summary: Mutations in MCM7 are identified as a novel cause of autosomal recessive primary microcephaly (MCPH) and intellectual disability, highlighting its crucial role in nervous system development. The expression pattern of MCM7 is consistent in mouse and human cells, affecting cell viability and proliferation.
JOURNAL OF MEDICAL GENETICS
(2022)
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
Biochemical Research Methods
Emily H. Canessa, Mansi V. Goswami, Tchilabalo D. Alayi, Eric P. Hoffman, Yetrib Hathout
JOURNAL OF MASS SPECTROMETRY
(2020)
Article
Genetics & Heredity
Matthias Pergande, Susanne Motameny, Oezkan Oezdemir, Mona Kreutzer, Haicui Wang, Huelya-Sevcan Daimagueler, Kerstin Becker, Mert Karakaya, Harald Ehrhardt, Nursel Elcioglu, Slavica Ostojic, Cho-Ming Chao, Amit Kawalia, Ozgur Duman, Anne Koy, Andreas Hahn, Jens Reimann, Katharina Schoner, Anne Schaenzer, Jens H. Westhoff, Eva Maria Christina Schwaibold, Mireille Cossee, Marion Imbert-Bouteille, Harald von Pein, Goknur Haliloglu, Haluk Topaloglu, Janine Altmueller, Peter Nuernberg, Holger Thiele, Raoul Heller, Sebahattin Cirak
GENETICS IN MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Pietro Spitali, Irina Zaharieva, Stefan Bohringer, Monika Hiller, Amina Chaouch, Andreas Roos, Chiara Scotton, Mireille Claustres, Luca Bello, Craig M. McDonald, Eric P. Hoffman, Zaida Koeks, H. Eka Suchiman, Sebahattin Cirak, Mariacristina Scoto, Mojgan Reza, Peter A. C. 't Hoen, Erik H. Niks, Sylvie Tuffery-Giraud, Hanns Lochmueller, Alessandra Ferlini, Francesco Muntoni, Annemieke Aartsma-Rus, Alberto Dubrovsky, Andrew Kornberg, Kathryn North, Monique Ryan, Richard Webster, W. Douglas Biggar, Laura C. McAdam, Jean K. Mah, Hanna Kolski, V. Vishwanathan, S. Chidambaranathan, Yoram Nevo, Ksenija Gorni, Jose Carlo, Mar Tulinius, Timothy Lotze, Tulio E. Bertorini, John W. Day, Peter Karachunski, Paula R. Clemens, Hoda Abdel-Hamid, Jean Teasley, Nancy Kuntz, Sherilyn Driscoll, John B. Bodensteiner, Anne M. Connolly, Alan Pestronk, R. T. Abresch, Erik K. Henricson, Nanette C. Joyce, Avital Cnaan, Heather Gordish-Dressmsn, Lauren P. Morgenroth, Robert Leshner, Carolina Tesi-Rocha, Mathula Thangarajh, Tina Duong
EUROPEAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Endocrinology & Metabolism
Donia Macartney-Coxson, Kirsty Danielson, Jane Clapham, Miles C. Benton, Alice Johnston, Angela Jones, Odette Shaw, Ronald D. Hagan, Eric P. Hoffman, Mark Hayes, Jacquie Harper, Michael A. Langston, Richard S. Stubbs
Article
Rheumatology
Travis B. Kinder, Christopher R. Heier, Christopher B. Tully, Jack H. Van der Muelen, Eric P. Hoffman, Kanneboyina Nagaraju, Alyson A. Fiorillo
ARTHRITIS & RHEUMATOLOGY
(2020)
Correction
Genetics & Heredity
Matthias Pergande, Susanne Motameny, Ozkan Ozdemir, Mona Kreutzer, Haicui Wang, Huelya-Sevcan Daimaguler, Kerstin Becker, Mert Karakaya, Harald Ehrhardt, Nursel Elcioglu, Slavica Ostojic, Cho-Ming Chao, Amit Kawalia, Ozgur Duman, Anne Koy, Andreas Hahn, Jens Reimann, Katharina Schoner, Anne Schanzer, Jens H. Westhoff, Eva Maria Christina Schwaibold, Mireille Cossee, Marion Imbert-Bouteille, Harald von Pein, Goknur Haliloglu, Haluk Topaloglu, Janine Altmuller, Peter Nurnberg, Holger Thiele, Raoul Heller, Sebahattin Cirak
GENETICS IN MEDICINE
(2020)
Article
Pharmacology & Pharmacy
Xiaonan Li, Laurie S. Conklin, John van den Anker, Eric P. Hoffman, Paula R. Clemens, William J. Jusko
JOURNAL OF CLINICAL PHARMACOLOGY
(2020)
Article
Clinical Neurology
Paula R. Clemens, Vamshi K. Rao, Anne M. Connolly, Amy D. Harper, Jean K. Mah, Edward C. Smith, Craig M. McDonald, Craig M. Zaidman, Lauren P. Morgenroth, Hironori Osaki, Youhei Satou, Taishi Yamashita, Eric P. Hoffman
Article
Clinical Neurology
Luca Bello, Grazia D'Angelo, Matteo Villa, Aurora Fusto, Sara Vianello, Beatrice Merlo, Daniele Sabbatini, Andrea Barp, Sandra Gandossini, Francesca Magri, Giacomo P. Comi, Marina Pedemonte, Paola Tacchetti, Valentina Lanzillotta, Federica Trucco, Adele D'Amico, Enrico Bertini, Guja Astrea, Luisa Politano, Riccardo Masson, Giovanni Baranello, Emilio Albamonte, Elisa De Mattia, Fabrizio Rao, Valeria A. Sansone, Stefano Previtali, Sonia Messina, Gian Luca Vita, Angela Berardinelli, Tiziana Mongini, Antonella Pini, Marika Pane, Eugenio Mercuri, Andrea Vianello, Claudio Bruno, Eric P. Hoffman, Lauren Morgenroth, Heather Gordish-Dressman, Craig M. McDonald, Elena Pegoraro
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2020)
Article
Medicine, General & Internal
Edward C. Smith, Laurie S. Conklin, Eric P. Hoffman, Paula R. Clemens, Jean K. Mah, Richard S. Finkel, Michela Guglieri, Mar Tulinius, Yoram Nevo, Monique M. Ryan, Richard Webster, Diana Castro, Nancy L. Kuntz, Laurie Kerchner, Lauren P. Morgenroth, Adrienne Arrieta, Maya Shimony, Mark Jaros, Phil Shale, Heather Gordish-Dressman, Laura Hagerty, Utkarsh J. Dang, Jesse M. Damsker, Benjamin D. Schwartz, Laurel J. Mengle-Gaw, Craig M. McDonald
Correction
Genetics & Heredity
Shereen G. Ghosh, Kerstin Becker, He Huang, Tracy D. Salazar, Guoliang Chai, Vincenzo Salpietro, Lihadh Al-Gazali, Quinten Waisfisz, Haicui Wang, Keith K. Vaux, Valentina Stanley, Andreea Manole, Ugur Akpulat, Marjan M. Weiss, Stephanie Efthymiou, Michael G. Hanna, Carlo Minetti, Pasquale Striano, Livia Pisciotta, Elisa De Grandis, Janine Altmuller, Lisa Weixler, Peter Nurnberg, Holger Thiele, Uluc Yis, Tuncay Derya Okur, Ayse Ipek Polat, Nafise Amiri, Mohammad Doosti, Ehsan Ghayoor Karimani, Mehran B. Toosi, Gabriel Haddad, Mert Karakaya, Brunhilde Wirth, Johanna M. van Hagen, Nicole I. Wolf, Reza Maroofian, Henry Houlden, Sebahattin Cirak, Joseph G. Gleeson
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Joanna Schneider, Devakumar Sundaravinayagam, Alexander Blume, Andreas Marg, Stefanie Grunwald, Eric Metzler, Helena Escobar, Stefanie Muethel, Haicui Wang, Tobias Wollersheim, Steffen Weber-Carstens, Altuna Akalin, Michela Di Virgilio, Baris Tursun, Simone Spuler
Summary: Critical illness myopathy (CIM) is a devastating muscle-wasting disease that has a significant impact on healthcare costs and quality of life. Impairment of muscle stem cells (MuSC) and epigenetic alterations may contribute to the incomplete recovery observed in CIM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Haicui Wang, Anne Krause, Helena Escobar, Stefanie Muethel, Eric Metzler, Simone Spuler
Summary: LMNA-related muscular dystrophy is a progressive disorder that can be corrected by gene editing using CRISPR/Cas9 tools. In this study, the researchers induced lamin A/C expression in patient-derived induced pluripotent stem cells (iPSCs) and successfully repaired the LMNA mutation using a precise gene editing approach. The findings demonstrate the potential therapeutic effect of CRISPR/Cas9-mediated gene correction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Sergey V. Prykhozhij, Lucia Caceres, Kevin Ban, Anna Cordeiro-Santanach, Kanneboyina Nagaraju, Eric P. Hoffman, Jason N. Berman
Summary: Limb-Girdle Muscular Dystrophy Type R1 (LGMDR1) is caused by CAPN3 mutations leading to progressive muscle weakness. The study generated zebrafish mutants to model LGMDR1 and found that capn3b is expressed in muscle. These mutants represent a novel model for studying muscle repair and remodeling, and as a preclinical tool for therapeutics and behavioral screening in LGMDR1.
Editorial Material
Medicine, Research & Experimental
Eric P. Hoffman
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)