Article
Clinical Neurology
Andrea Cortese, Riccardo Curro, Riccardo Ronco, Julian Blake, Alex M. Rossor, Enrico Bugiardini, Matilde Laura, Tom Warner, Tarek Yousry, Roy Poh, James Polke, Adriana Rebelo, Maike F. Dohrn, Mario Saporta, Henry Houlden, Stephan Zuchner, Mary M. Reilly
Summary: Mutations in the CRYAB gene have been associated with myofibrillar myopathy, dilated cardiomyopathy, and cataracts. This study reports peripheral neuropathy as a novel phenotype associated with CRYAB, particularly in cases with late onset CMT2 and congenital cataracts.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Tara C. Tassin, Barbara Barylko, Per Niklas Hedde, Yan Chen, Derk D. Binns, Nicholas G. James, Joachim D. Mueller, David M. Jameson, Ronald Taussig, Joseph P. Albanesi
Summary: Mutations in the DNM2 gene are associated with motor disorders affecting nerve and muscle, such as CMT and CNM; CMT and CNM mutations have distinct effects on DNM2 function, suggesting different pathogenic mechanisms and genetic overlap should be re-examined.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Marina Stavrou, Irene Sargiannidou, Elena Georgiou, Alexia Kagiava, Kleopas A. Kleopa
Summary: CMT disease is a genetically heterogeneous disorder affecting the peripheral nerves, with diverse molecular genetic mechanisms discovered over the past three decades. There are currently various treatment approaches in preclinical testing and clinical trials, including disease-specific targeted therapies and treatments targeting common pathways shared by different CMT types. As promising treatments advance to clinical translation, optimizing outcome measures, novel biomarkers, and appropriate trial designs are crucial to facilitate successful testing and validation of novel treatments for CMT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Rafael Sivera, Vincenzo Lupo, Marina Frasquet, Herminia Argente-Escrig, Jorge Alonso-Perez, Jordi Diaz-Manera, Luis Querol, Maria del Mar Garcia-Romero, Samuel Ignacio Pascual, Tania Garcia-Sobrino, Carmen Paradas, Juan Francisco Vazquez-Costa, Nuria Muelas, Elvira Millet, Juan Jesus Vilchez, Carmen Espinos, Teresa Sevilla
Summary: This study identified 15 patients with CMT2Z caused by MORC2 mutations in Spain, with most exhibiting a scapuloperoneal phenotype and a few showing a neurodevelopmental phenotype. The findings suggest a diverse spectrum of disease characteristics and clinical presentations.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Cara R. Schiavon, Gerald S. Shadel, Uri Manor
Summary: CMT disease is a progressive, inherited neurological disorder associated with mutations in at least 80 different genes. Clinical manifestations typically involve peripheral neurons, with some mutations potentially leading to mitochondrial mobility defects, suggesting a common underlying disease mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Karen Libberecht, Tim Vangansewinkel, Ludo Van Den Bosch, Ivo Lambrichts, Esther Wolfs
Summary: This article reviews the role of protein quality control systems in CMT1 and introduces potential treatment strategies to restore proteostasis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Genetics & Heredity
Yuji Okamoto, Hiroshi Takashima
Summary: Charcot-Marie-Tooth disease (CMT) is the most common genetically transmitted neuromuscular condition without effective pharmacological treatments. The genetic heterogeneity of CMT poses a significant barrier to comprehensive therapies. This review discusses prospective therapeutic strategies for common CMT variants and evaluates the progress in gene therapy techniques, which have the potential to advance future research.
Article
Clinical Neurology
Adriana P. Rebelo, Andrea Cortese, Amit Abraham, Yael Eshed-Eisenbach, Gal Shner, Anna Vainshtein, Elena Buglo, Vladimir Camarena, Gabriel Gaidosh, Ramin Shiekhattar, Lisa Abreu, Steve Courel, Dennis K. Burns, Yunhong Bai, Chelsea Bacon, Shawna M. E. Feely, Diana Castro, Elior Peles, Mary M. Reilly, Michael E. Shy, Stephan Zuchner
Summary: The CADM family of proteins mediate direct contact and interaction between axons and glia, with mutations in CADM3 potentially causing abnormal axon-glia interaction and disease manifestation in CMT patients.
Article
Clinical Neurology
Elena Abati, Stefania Magri, Megi Meneri, Giulia Manenti, Daniele Velardo, Francesca Balistreri, Chiara Pisciotta, Paola Saveri, Nereo Bresolin, Giacomo Pietro Comi, Dario Ronchi, Davide Pareyson, Franco Taroni, Stefania Corti
Summary: This study identified two cases of biallelic HSPB1 p.S135F and p.R136L mutations in two families, confirming their association with severe CMT2F/dHMN and a strictly dominant inheritance pattern.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Marta Bellofatto, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Daniela Calabrese, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Chiara Pisciotta, Davide Pareyson
Summary: This study investigated fatigue in CMT patients and found that 36% of the patients experienced abnormal fatigue. Abnormal fatigue was correlated with disease severity, anxiety, depression, sleepiness, and obesity. Therefore, the management of CMT patients should involve treating fatigue and addressing other factors such as anxiety, depression, sleepiness, and obesity.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Marta Bellofatto, Luca Gentile, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano Previtali, Marina Scarlato, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Flavio Villani, Eleonora Cavalca, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Giuseppe Didato, Chiara Pisciotta, Davide Pareyson, CMT Network
Summary: This study investigated the presence of sleep abnormalities in Charcot-Marie-Tooth disease (CMT) patients and their correlation with disease severity and characteristics. The results showed that CMT patients had poor sleep quality and daytime somnolence, which were associated with anxiety, depression, and fatigue.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Marta Bellofatto, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Daniela Calabrese, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Chiara Pisciotta, Davide Pareyson
Summary: This study investigated the presence of fatigue and its correlations in Charcot-Marie-Tooth disease (CMT). The results showed that 36% of the patients had abnormal fatigue, which was correlated with disease severity, anxiety, depression, sleepiness, and obesity. Therefore, the management of CMT patients should include treatment for fatigue and its different generators.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Ru-Ying Yuan, Zi-Ling Ye, Xiao-Rong Zhang, Liu-Qing Xu, Jin He
Summary: The study confirmed SORD mutations as a causative factor for CMT and expanded the mutational and phenotypic spectrum of SORD-related CMT.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Matthew J. Jennings, Alexia Kagiava, Leen Vendredy, Emily L. Spaulding, Marina Stavrou, Denisa Hathazi, Anika Gruneboom, Vicky De Winter, Burkhard Gess, Ulrike Schara, Oksana Pogoryelova, Hanns Lochmuller, Christoph H. Borchers, Andreas Roos, Robert W. Burgess, Vincent Timmerman, Kleopas A. Kleopa, Rita Horvath
Summary: By studying the proteins in the serum of CMT patients and mouse models, potential biomarkers for CMT are identified, which can be used to assess disease severity and track treatment effects. In addition, elevation of complement proteins in CMT suggests a potential therapeutic target.
Article
Clinical Neurology
Fabien Hauw, Guillaume Fargeot, David Adams, Shahram Attarian, Cecile Cauquil, Jean-Baptiste Chanson, Alain Creange, Thierry Gendre, Kumaran Deiva, Emilien Delmont, Bruno Francou, Steeve Genestet, Thierry Kuntzer, Philippe Latour, Gwendal Le Masson, Laurent Magy, Clotilde Nardin, Francois Ochsner, Guilhem Sole, Tanya Stojkovic, Thierry Maisonobe, Celine Tard, Peter van den Berghe, Andoni Echaniz-Laguna
Summary: This study found that 35 out of 1104 patients initially diagnosed with CIDP actually had CMT. The cost of treating these misdiagnosed patients was significantly higher than the cost of performing CMT genetic analysis in the larger patient group, indicating the importance of utilizing CMT genetic investigations before diagnosing CIDP.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Correction
Cell Biology
Cheng-I J. Ma, Yitong Yang, Taeah Kim, Chang Hua Chen, Gordon Polevoy, Miluska Vissa, Jason Burgess, Julie A. Brill
JOURNAL OF CELL BIOLOGY
(2021)
Article
Pediatrics
Reem Abdwani, Eiman Abdalla, Buthaina Al Masilhi, Asma Shalaby, Al Munthir Al Mawali
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2022)
Article
Genetics & Heredity
Bushra Al-Shamsi, Ghalia Al-Kasbi, Adila Al-Kindi, Zandre Bruwer, Khalsa Al-Kharusi, Almundher Al-Maawali
Summary: Bilateral renal agenesis is a perinatal lethal renal disease, causally associated with pathogenic variants in genes like ITGA8, GREB1L, FGF20, and GFRA1. The latest study confirms the role of GFRA1 in lethal nonsyndromic bilateral renal agenesis in humans.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Correction
Cell Biology
Cheng-I J. Ma, Yitong Yang, Taeah Kim, Chang Hua Chen, Gordon Polevoy, Miluska Vissa, Jason Burgess, Julie A. Brill
JOURNAL OF CELL BIOLOGY
(2022)
Article
Genetics & Heredity
Zandre Bruwer, Salwa Al Ubaidani, Khalsa Al Kharusi, Fathiya Al Murshedi, Almundher Al-Maawali, Abeer Al Sayegh, Adila Al Kindy, Nihal Al Riyami, Tamima Al Dughaishi, Mouza Al Salmani, Nadia Al Hashmi, Maryam Al Shehhi, Badriya Al Fahdi, Sumaya Al Amri, Khalid Al-Thihli
Summary: This study reports on the acceptance of prenatal diagnosis for single gene disorders in Omani Muslim couples, indicating that it is an acceptable reproductive option to prevent genetic disorders.
JOURNAL OF COMMUNITY GENETICS
(2022)
Article
Genetics & Heredity
Martin Broly, Bogdan Polevoda, Kamel M. Awayda, Ning Tong, Jenna Lentini, Thomas Besnard, Wallid Deb, Declan O'Rourke, Julia Baptista, Sian Ellard, Mohammed Almannai, Mais Hashem, Ferdous Abdulwahab, Hanan Shamseldin, Saeed Al-Tala, Fowzan S. Alkuraya, Alberta Leon, Rosa L. E. van Loon, Alessandra Ferlini, Mariabeatrice Sanchini, Stefania Bigoni, Andrea Ciorba, Hans van Bokhoven, Zafar Iqbal, Almundher Al-Maawali, Fathiya Al-Murshedi, Anuradha Ganesh, Watfa Al-Mamari, Sze Chern Lim, Lynn S. Pais, Natasha Brown, Saima Riazuddin, Stephane Bezieau, Dragony Fu, Bertrand Isidor, Benjamin Cogne, Mitchell R. O'Connell
Summary: Covalent tRNA modifications have diverse roles in tRNA stability, folding, translation rate and fidelity, and various cellular processes. Mutations in the THUMPDI gene, involved in tRNA N4-acetylcytidine modification, have been linked to intellectual disability. This study presents individuals with rare loss-of-function variants in THUMPDI, showing common features of developmental delay, intellectual deficiency, behavioral abnormalities, facial dysmorphism, and ophthalmological abnormalities. Functional analysis demonstrates that THUMPDI variants result in a loss of tRNA modification, leading to syndromic intellectual disability.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Marion Coolen, Nami Altin, Karthyayani Rajamani, Eva Pereira, Karine Siquier-Pernet, Emilia Puig Lombardi, Nadjeda Moreno, Giulia Barcia, Marianne Yvert, Annie Laquerriere, Aurore Pouliet, Patrick Nitschke, Nathalie Boddaert, Antonio Rausell, Ferechte Razavi, Alexandra Afenjar, Thierry Billette de Villemeur, Almundher Al-Maawali, Khalid Al-Thihli, Julia Baptista, Ana Beleza-Meireles, Catherine Garel, Marine Legendre, Antoinette Gelot, Lydie Burglen, Sebastien Moutton, Vincent Cantagrel
Summary: Pontocerebellar hypoplasias (PCHs) are congenital disorders characterized by cerebellar and brainstem abnormalities. Recent research identified bi-allelic mutations in PRDM13 as causing olivopontocerebellar hypoplasia syndrome, suggesting transcriptional dysregulation in neuronal fate specification may contribute to the condition.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Abdulhamid Al-Hinai, Samiya Al-Hashmi, Anuradha Ganesh, Nadia Al-Hashmi, Abeer Al-Saegh, Watfa Al-Mamari, Fathiya Al-Murshedi, Khalid Al-Thihli, Adila Al-Kindi, Almundher Al-Maawali
Summary: Alazami syndrome is a rare autosomal recessive genetic disorder characterized by severe growth restriction, intellectual disability, and distinctive facial features. This study reports on 12 patients from eight unrelated families, expanding the clinical and molecular characteristics of the syndrome and identifying additional phenotypic features.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Khalid Al-Waili, Khalid Al-Rasadi, Muna Al-Bulushi, Mohammed Habais, Abdullah Al-Mujaini, Saif Al-Yaarubi, Antoine Rimbert, Razan Zadjali, Pegah Moradi Khaniabadi, Hamida Al-Barwani, Sana Hasary, Zayana M. Al-Dahmani, Hala Al-Badi, Almundher Al-Maawali, Fahad Zadjali
Summary: This study identified novel genetic mutations in F-HTG patients of Arab ancestry in Oman, suggesting a founder effect and genetic uniqueness in this population. These findings highlight the importance of further analysis and counseling for F-HTG patients in the Middle East, particularly in populations with high rates of consanguinity.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Luis Carlos Tabara, Fatema Al-Salmi, Reza Maroofian, Amna Mohammed Al-Futaisi, Fathiya Al-Murshedi, Joanna Kennedy, Jacob O. Day, Thomas Courtin, Aisha Al-Khayat, Hamid Galedari, Neda Mazaheri, Margherita Protasoni, Mark Johnson, Joseph S. Leslie, Claire G. Salter, Lettie E. Rawlins, James Fasham, Almundher Al-Maawali, Nikol Voutsina, Perrine Charles, Laura Harrold, Boris Keren, Edmund R. S. Kunji, Barbara Vona, Gholamreza Jelodar, Alireza Sedaghat, Gholamreza Shariati, Henry Houlden, Andrew H. Crosby, Julien Prudent, Emma L. Baple
Summary: Hereditary spastic paraplegia (HSP), a genetically diverse neurodegenerative disease, can be classified as pure or complex forms. Biallelic variants in the TMEM63C gene were identified in individuals with HSP and mild intellectual disability. Further analysis showed that TMEM63C plays a role in regulating both endoplasmic reticulum and mitochondrial morphologies.
Article
Immunology
Salem Al-Tamemi, Zaid Alhinai, Najwa Al-Rahbi, Raghad Al-Abdawani, Laila Al-Yazidi, Jalila Al-Shekaili, Mahmood Al-Kindi, Almundher Al-Maawali
Summary: This study reports a rare case of SCID in a patient from the Middle East, caused by a novel homozygous mutation in the BCL10 gene. The patient exhibited typical symptoms of SCID and ultimately died due to severe infection.
CLINICAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Scott Frendo-Cumbo, Taoyingnan Li, Dustin A. Ammendolia, Etienne Coyaud, Estelle M. N. Laurent, Yuan Liu, Philip J. Bilan, Gordon Polevoy, Brian Raught, Julie A. Brill, Amira Klip, John H. Brumell
Summary: Cell proliferation is regulated by growth factors insulin and IGF1. The study identified DCAF7 as an interactor of IRS1, a mediator of insulin/IGF1 signaling, that regulates cell proliferation and cell cycle through the IRS1-FOXO1 signaling pathway. DCAF7 knockdown led to cell cycle arrest and reduced cell proliferation.
Article
Developmental Biology
Lisa Shao, Jaclyn M. Fingerhut, Brook L. Falk, Hong Han, Giovanna Maldonado, Yuemeng Qiao, Vincent Lee, Elizabeth Hall, Liang Chen, Gordon Polevoy, Greco Hernandez, Paul Lasko, Julie A. Brill
Summary: Drosophila sperm development involves extensive post-transcriptional regulation, with eIF4E-5 playing a crucial role. Mutations in eIF4E-5 lead to defects in spermatid polarization, individualization, and sperm production. eIF4E-5 regulates non-apoptotic caspase activity during individualization by promoting the accumulation of Soti, an E3 ubiquitin ligase inhibitor. This study expands our understanding of the diverse roles of non-canonical eIF4Es in spermatogenesis.
Correction
Multidisciplinary Sciences
Scott Frendo-Cumbo, Taoyingnan Li, Dustin A. Ammendolia, Etienne Coyaud, Estelle M. N. Laurent, Yuan Liu, Philip J. Bilan, Gordon Polevoy, Brian Raught, Julie A. Brill, Amira Klip, John H. Brumell
Article
Biology
Amelie A. Raz, Gabriela S. Vida, Sarah R. Stern, Sharvani Mahadevaraju, Jaclyn M. Fingerhut, Jennifer M. Viveiros, Soumitra Pal, Jasmine R. Grey, Mara R. Grace, Cameron W. Berry, Hongjie Li, Jasper Janssens, Wouter Saelens, Zhantao Shao, Chun Hu, Yukiko M. Yamshita, Teresa Przytycka, Brian Oliver, Julie A. Brill, Henry Krause, Erika L. Matunis, Helen White-Cooper, Stephen DiNardo, Margaret T. Fuller, Michael Buszczak
Summary: We provide a comprehensive single nucleus and single cell RNA-seq resource for spermatogenesis in Drosophila, obtained from the analysis of adult testis single nucleus RNA-seq (snRNA-seq) data. This dataset includes over 44,000 nuclei and 6000 cells, allowing for the identification of rare cell types, mapping of intermediate steps in differentiation, and the potential discovery of new factors impacting fertility or controlling differentiation.