Article
Clinical Neurology
Arnaud Jacquier, Julian Theuriet, Fanny Fontaine, Valentine Mosbach, Nicolas Lacoste, Shams Ribault, Valerie Risson, Julien Carras, Laurent Coudert, Thomas Simonet, Philippe Latour, Tanya Stojkovic, Juliette Piard, Anne Cosson, Gaetan Lesca, Francoise Bouhour, Stephane Allouche, Helene Puccio, Antoine Pegat, Laurent Schaeffer
Summary: Jacquier et al. identified a homozygous variant in the COQ7 gene in a family with distal hereditary motor neuropathy. This variant leads to a decrease in coenzyme Q10 production, causing impaired mitochondrial metabolism. Coenzyme Q10 supplementation may serve as a potential treatment for this disorder.
Article
Clinical Neurology
Adriana P. Rebelo, Pedro J. Tomaselli, Jessica Medina, Ying Wang, Maike F. Dohrn, Eva Nyvltova, Matt C. Danzi, Mark Garrett, Sean E. Smith, Alan Pestronk, Chengcheng Li, Ariel Ruiz, Elizabeth Jacobs, Shawna M. E. Feely, Marcondes C. Franca Jr, Marcus Gomes, Diogo F. Santos, Surinder Kumar, David B. Lombard, Mario Saporta, Siegfried Hekimi, Antoni Barrientos, Conrad Weihl, Michael E. Shy, Wilson Marques, Stephan Zuchner
Summary: Rebelo et al. identified COQ7 biallelic variants in nine families with distal hereditary motor neuropathy with upper motor neuron involvement, expanding the clinical phenotype of this gene. COQ7 mutations have been previously associated with primary CoQ(10) deficiency, and our findings indicate a molecular pathway involving CoQ(10) biosynthesis deficiency and mitochondrial dysfunction in patients with distal hereditary motor neuropathy. Fibroblasts from patients showed protein instability, reduced CoQ(10) levels, and abnormal accumulation of the biosynthetic precursor DMQ(10). Further studies are needed to evaluate the potential benefits of CoQ(10) supplementation in the clinical outcome of the disease.
Article
Clinical Neurology
Marina Frasquet, Ricard Rojas-Garcia, Herminia Argente-Escrig, Juan Francisco Vazquez-Costa, Nuria Muelas, Juan Jesus Vilchez, Rafael Sivera, Elvira Millet, Marisa Barreiro, Jordi Diaz-Manera, Janina Turon-Sans, Elena Cortes-Vicente, Luis Querol, Laura Ramirez-Jimenez, Dolores Martinez-Rubio, Ana Sanchez-Monteagudo, Carmen Espinos, Teresa Sevilla, Vincenzo Lupo
Summary: This study confirms the genetic heterogeneity of distal hereditary motor neuropathies and establishes biallelic SORD mutations as a cause of the disease in different populations. The study also reveals the genetic diagnostic rate, most common genetic mutations, and prevalence of the disease.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Anthony N. Cutrupi, Ramesh K. Narayanan, Gonzalo Perez-Siles, Bianca R. Grosz, Kaitao Lai, Alexandra Boyling, Melina Ellis, Ruby C. Y. Lin, Brent Neumann, Di Mao, Motonari Uesugi, Garth A. Nicholson, Steve Vucic, Mario A. Saporta, Marina L. Kennerson
Summary: This study identifies a novel gene-intergenic fusion transcript (UBE3C-IF) associated with distal hereditary motor neuropathy 1 (DHMN1). The UBE3C-IF transcript leads to decreased UBE3C protein levels in DHMN1 patient-derived motor neurons and causes synaptic transmission deficits and susceptibility to heat stress in a Caenorhabditis elegans model.
Article
Cell Biology
Luis Aguila, Joao Suzuki, Amanda B. T. Hill, Monica Garcia, Karine de Mattos, Jacinthe Therrien, Lawrence C. Smith
Summary: Mammalian uniparental embryos serve as efficient models for genome imprinting research, and in this study, various methods for producing bovine haploid androgenetic embryos were analyzed. Results indicate that while androgenetic haploidy does not disturb early development, aberrant expression of key factors involved in X chromosome activity and genomic imprinting may be associated with the inefficient development of bovine haploid androgenetic embryos.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Xiaoxuan Liu, Ji He, Mubalake Yilihamu, Xiaohui Duan, Dongsheng Fan
Summary: Biallelic mutations in the SORD gene are a common cause of autosomal recessive axonal Charcot-Marie-Tooth (CMT2) and distal hereditary motor neuropathy (dHMN) in a large Chinese cohort. Patients with SORD mutations present with distal weakness, atrophy in the lower limb, and some may also have minor clinical sensory abnormalities and small fiber neuropathy.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Jingfei Zhang, Hong Wang, Wenjie Liu, Juan Wang, Jing Zhang, Xueli Chang, Shan Huang, Xiaomin Pang, Junhong Guo, Qiuhong Wang, Wei Zhang
Summary: A novel missense mutation c.279G>C (Q93H) in DCTN1 was identified as the candidate loci causing both familial dHMN7B and Perry syndrome, expanding the clinical and pathogenic spectrum of DCTN1 gene.
NEUROLOGICAL SCIENCES
(2021)
Article
Oncology
Koya Yoshizawa, Akira Matsura, Masaya Shimada, Sumire Ishida-Ishihara, Fuyu Sato, Takahiro Yamamoto, Kan Yaguchi, Eiji Kawamoto, Taruho Kuroda, Kazuya Matsuo, Nobuyuki Tamaoki, Ryuichi Sakai, Yasuhito Shimada, Mithilesh Mishra, Ryota Uehara
Summary: Tetraploid cells are more susceptible to CENP-E inhibitors and the inhibitors can selectively suppress the growth of tetraploid cells.
MOLECULAR ONCOLOGY
(2023)
Article
Neurosciences
Laura Behrendt, Christian Hoischen, Christoph Kaether
Summary: Mutations in the ER-network forming GTPase atlastin3 (ATL3) can cause axon degeneration of sensory neurons. The mutated ATL3 is excluded from distal axons by a selective barrier at the axon initial segment. Actin-depolymerization partially restores the transport of mutated ATL3 into distal axons.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Clinical Neurology
Hiroya Naruse, So Okubo, Atsushi Sudo, Jun Mitsui, Takashi Mikata, Hiroyuki Ishiura, Shinichi Morishita, Shoji Tsuji, Tatsushi Toda
Summary: This study describes the clinical features of a family with late-onset distal hereditary motor neuropathy (dHMN) carrying the Pro39Leu variant of HSPB1. The patients exhibited distal muscle weakness with lower extremity predominance and no obvious sensory deficits. The study suggests that HSPB1 variants may cause late-onset dHMN with a broader spectrum of clinical manifestations, including concomitant sensory deficits.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Carlos Pablo de Fuenmayor-Fernandez de la Hoz, Vincenzo Lupo, Laura Bermejo-Guerrero, Paloma Martin-Jimenez, Aurelio Hernandez-Lain, Montse Olive, Eduard Gallardo, Jesus Esteban-Perez, Carmen Espinos, Cristina Dominguez-Gonzalez
Summary: This study describes a new phenotype associated with a novel variant in BAG3 gene, presenting as autosomal dominant adult-onset distal hereditary motor neuronopathy. The findings expand the phenotypic spectrum of BAG3-related disorders and highlight the importance of considering BAG3 gene variants in the differential diagnosis of distal hereditary motor neuronopathies.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Bin Chen, Zaiqiang Zhang, Cuiping Zhang, Songtao Niu, Hua Pan, Gehong Dong, Xingao Wang
Summary: This study describes a patient with clinical manifestations and related gene mutations, expanding the pathological and mutation spectrum of SORD-related neuropathy.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2022)
Article
Multidisciplinary Sciences
Takeshi Yamamotoya, Shun Hasei, Yasuyuki Akasaka, Yukino Ohata, Yusuke Nakatsu, Machi Kanna, Midori Fujishiro, Hideyuki Sakoda, Hiraku Ono, Akifumi Kushiyama, Hidemi Misawa, Tomoichiro Asano
Summary: Loss of Trk-fused gene (TFG) in motor neurons leads to neuromuscular junction (NMJ) degeneration and muscle atrophy, while lack of TFG in muscles may have additional effects. These findings are important for understanding the mechanisms associated with neurodegenerative diseases.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Majed Alluqmani, Sulman Basit
Summary: This study identified a potential genetic defect in a family with autosomal recessive asymmetric hereditary motor neuropathy. The study reports the first SORD mutation from Saudi Arabia and expands the phenotypic spectrum of SORD mutation.
BMC MEDICAL GENOMICS
(2022)
Article
Clinical Neurology
Lior Greenbaum, Merav Ben-David, Vera Nikitin, Orna Gera, Ortal Barel, Adi Hersalis-Eldar, Jana Shamash, Noam Shimshoviz, Haike Reznik-Wolf, Mordechai Shohat, Dan Dominissini, Elon Pras, Amir Dori
Summary: The HSPB1 c.407G>G (p.Arg136Leu) mutation causes an adult-onset, predominantly motor, axonal neuropathy in individuals of Jewish Iranian descent. Variable manifestations are noticed, and sensory involvement is more prominent in prolonged disease duration.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Cell Biology
Sonia Sanz Munoz, Martin Engel, Rachelle Balez, Dzung Do-Ha, Mauricio Castro Cabral-da-Silva, Damian Hernandez, Tracey Berg, Jennifer A. Fifita, Natalie Grima, Shu Yang, Ian P. Blair, Garth Nicholson, Anthony L. Cook, Alex W. Hewitt, Alice Pebay, Lezanne Ooi
Article
Clinical Neurology
Sindhu Ramchandren, Tong Tong Wu, Richard S. Finkel, Carly E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. Reilly, Timothy Estilow Ot, Michael E. Shy
Summary: The study identified 6 domains relevant to quality of life in children with CMT through systematic literature reviews and analysis of generic QOL measures. A total of 60 items corresponding to those domains were developed and underwent rigorous psychometric testing to develop a reliable and valid pediatric CMT-specific quality of life outcome measure.
ANNALS OF NEUROLOGY
(2021)
Article
Geriatrics & Gerontology
Sandrine Chan Moi Fat, Emily P. McCann, Kelly L. Williams, Lyndal Henden, Natalie A. Twine, Denis C. Bauer, Roger Pamphlett, Matthew C. Kiernan, Dominic B. Rowe, Garth A. Nicholson, Jennifer A. Fifita, Ian P. Blair
Summary: Mutations in GLT8D1 and ARPP21 are not a common cause of ALS in Australian familial and sporadic cohorts, as no novel mutations were identified in either gene.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Ramita Dewan, Ruth Chia, Jinhui Ding, Richard A. Hickman, Thor D. Stein, Yevgeniya Abramzon, Sarah Ahmed, Marya S. Sabir, Makayla K. Portley, Arianna Tucci, Kristina Ibanez, F. N. U. Shankaracharya, Pamela Keagle, Giacomina Rossi, Paola Caroppo, Fabrizio Tagliavini, Maria L. Waldo, Per M. Johansson, Christer F. Nilsson, James B. Rowe, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Edwin Jabbari, Coralie Viollet, Jonathan D. Glass, Andrew B. Singleton, Vincenzo Silani, Owen A. Ross, Mina Ryten, Ali Torkamani, Toshiko Tanaka, Luigi Ferrucci, Susan M. Resnick, Stuart Pickering-Brown, Christopher B. Brady, Neil Kowal, John A. Hardy, Vivianna Van Deerlin, Jean Paul Vonsattel, Matthew B. Harms, Huw R. Morris, Raffaele Ferrari, John E. Landers, Adriano Chio, J. Raphael Gibbs, Clifton L. Dalgard, Sonja W. Scholz, Bryan J. Traynor
Summary: Researchers analyzed whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 LBD patients, and 3,158 neurologically healthy subjects, identifying pathogenic HTT gene expansions in a small percentage of FTD/ALS patients but not in the LBD or healthy groups. Postmortem evaluations supported an etiological relationship between HTT repeat expansions and FTD/ALS syndromes, suggesting the importance of genetic screening for HTT repeat expansions in FTD/ALS patients.
Article
Clinical Neurology
Paige Howard, Shawna M. E. Feely, Tiffany Grider, Alexa Bacha, Marina Scarlato, Raffaella Fazio, Angelo Quattrini, Michael E. Shy, Stefano C. Previtali
Summary: Mutations in the Myelin Protein Zero (MPZ) gene lead to CMT1B, with toxic gain of function from the mutant protein causing neuropathy, while some patients have haploinsufficiency in the MPZ gene, mainly presenting with sensory neuropathy.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2021)
Article
Biology
Alvaro Gonzalez Rajal, Kamila A. Marzec, Rachael A. McCloy, Max Nobis, Venessa Chin, Jordan F. Hastings, Kaitao Lai, Marina Kennerson, William E. Hughes, Vijesh Vaghjiani, Paul Timpson, Jason E. Cain, D. Neil Watkins, David R. Croucher, Andrew Burgess
Summary: The study identified a non-genetic mechanism of resistance in human lung adenocarcinoma that is dependent on the cell cycle stage at the time of cisplatin exposure, using RNA sequencing and biosensors to track single-cell fates.
Article
Clinical Neurology
Tiziana Cavallaro, Matteo Tagliapietra, Gian Maria Fabrizi, Yunhong Bai, Michael E. Shy, Jean-Michel Vallat
Summary: Hereditary neuropathies can be caused by mutations in genes expressed by Schwann cells or neurons, and may involve the central nervous system and other organs and tissues, with diagnostic methods revolutionizing due to advances in molecular genetics; skin biopsy has emerged as a minimally invasive method to provide clues to the pathophysiology and molecular pathology of inherited neuropathies.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2021)
Article
Genetics & Heredity
Bianca R. Grosz, John Svaren, Gonzalo Perez-Siles, Garth A. Nicholson, Marina L. Kennerson
Summary: This study assessed the IRES activity of the human GJB1 5' UTR and found no significant differences in expression levels between the wild-type UTR and the UTR with the c.-103C > T mutation, suggesting an alternate pathogenic mechanism for this non-coding mutation.
Editorial Material
Clinical Neurology
Tiziana Cavallaro, Matteo Tagliapietra, Gian Maria Fabrizi, Yunhong Bai, Michael E. Shy, Jean-Michel Vallat
Summary: The cover image is based on the Special Issue HEREDITARY NEUROPATHIES: A PATHOLOGICAL PERSPECTIVE by Tiziana Cavallaro et al., focusing on hereditary neuropathies from a pathological perspective.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2021)
Review
Clinical Neurology
Mary M. Reilly, David N. Herrmann, Davide Pareyson, Steven S. Scherer, Richard S. Finkel, Stephan Zuechner, Joshua Burns, Michael E. Shy
Summary: Heritable neurological disorders provide insights into disease mechanisms, facilitating the development of novel therapeutic approaches. The challenges of measuring disease progression in rare and slowly progressive neurogenetic diseases are addressed through the development of clinical outcome assessments and disease biomarkers in inherited peripheral neuropathies. It is proposed that carefully developed biomarkers from imaging, plasma, or skin can predict meaningful progression in functional and patient-reported outcome assessments, enabling feasible clinical trials within a shorter duration for these rare and ultra-rare disorders.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Tong Tong Wu, Richard S. S. Finkel, Carly E. E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. M. Reilly, Francesco Muntoni, Timothy Estilow, Michael E. E. Shy, Sindhu Ramchandren
Summary: This study developed and validated the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 with CMT, which is a reliable and valid measure of health-related QOL.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Tong Tong Wu, Richard Finkel, Carly E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. Reilly, Francesco Muntoni, Evelin Milev, Timothy Estilow, Michael E. Shy, Sindhu Ramchandren
Summary: The objective of this study was to evaluate the parent-proxy version of the pediatric Charcot Marie Tooth specific quality of life (pCMT-QOL) outcome instrument for children aged 7 or younger with CMT. The parent-proxy version of the pCMT-QOL outcome measure, known as the pCMT-QOL (0-7 years parent-proxy), was validated as a valid and sensitive proxy measure of health-related quality of life for children aged 0-7 years with CMT.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Christopher P. Ptak, Tabitha A. Peterson, Jesse B. Hopkins, Christopher A. Ahern, Michael E. Shy, Robert C. Piper
Summary: Mutations in MPZ can cause various neurological disorders, and the study focuses on understanding how MPZ functions and forms oligomeric assemblies.
Article
Clinical Neurology
Matthew Silsby, Con Yiannikas, Alessandro F. Fois, Marina L. Kennerson, Matthew C. Kiernan, Victor S. C. Fung, Steve Vucic
Summary: Neuropathic tremor is a common clinical feature in CMT1A, with distinct characteristics compared to essential tremor. Upper limb tremors were postural and kinetic, while lower limb tremors were postural and orthostatic. The frequency of upper limb tremors varied along the limb, with a lower frequency distally and a higher frequency proximally. Lower limb tremors had a consistent frequency and were unaffected by fatigue. Postural lower limb tremor was associated with imbalance.
JOURNAL OF NEUROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Marta F. Nabais, Simon M. Laws, Tian Lin, Costanza L. Vallerga, Nicola J. Armstrong, Ian P. Blair, John B. Kwok, Karen A. Mather, George D. Mellick, Perminder S. Sachdev, Leanne Wallace, Anjali K. Henders, Ramona A. J. Zwamborn, Paul J. Hop, Katie Lunnon, Ehsan Pishva, Janou A. Y. Roubroeks, Hilkka Soininen, Magda Tsolaki, Patrizia Mecocci, Simon Lovestone, Iwona Kloszewska, Bruno Vellas, Sarah Furlong, Fleur C. Garton, Robert D. Henderson, Susan Mathers, Pamela A. McCombe, Merrilee Needham, Shyuan T. Ngo, Garth Nicholson, Roger Pamphlett, Dominic B. Rowe, Frederik J. Steyn, Kelly L. Williams, Tim J. Anderson, Steven R. Bentley, John Dalrymple-Alford, Javed Fowder, Jacob Gratten, Glenda Halliday, Ian B. Hickie, Martin Kennedy, Simon J. G. Lewis, Grant W. Montgomery, John Pearson, Toni L. Pitcher, Peter Silburn, Futao Zhang, Peter M. Visscher, Jian Yang, Anna J. Stevenson, Robert F. Hillary, Riccardo E. Marioni, Sarah E. Harris, Ian J. Deary, Ashley R. Jones, Aleksey Shatunov, Alfredo Iacoangeli, Wouter van Rheenen, Leonard H. van den Berg, Pamela J. Shaw, Cristopher E. Shaw, Karen E. Morrison, Ammar Al-Chalabi, Jan H. Veldink, Eilis Hannon, Jonathan Mill, Naomi R. Wray, Allan F. McRae
Summary: This study identified shared differentially methylated positions in whole blood between neurodegenerative disorders, indicating shared pathogenic mechanisms. Immune abnormalities caused by different neurodegenerative diseases may be interrelated to some extent.
