Article
Cell Biology
Song Xiaozhen, Yuan Fan, Yuan Fang, Lan Xiaoping, Jia Jia, Xu Wuhen, Tang Xiaojun, Shen Jun, Chen Yucai, Zhang Hong, He Guang, Wu Shengnan
Summary: Two variants of the SEMA6B gene, occurring de novo in two patients, underlie early-onset epilepsy with different severity and treatment responses. One variant results in increased expression of a truncated protein, while the other affects a functional domain of SEMA6B. Both variants influence protein binding and suggest the potential mechanism of the SEMA6B-related disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Aibo Gao, Bin Gu, Juan Zhang, Chen Fang, Junlei Su, Haorong Li, Rulai Han, Lei Ye, Weiqing Wang, Guang Ning, Jiqiu Wang, Weiqiong Gu
Summary: The study found that the PAX4 R192H/S variants in East Asians are associated with early-onset diabetes and lead to decreased C-peptide levels, which may explain the difference in diabetes prevalence between East Asians and Europeans.
Article
Clinical Neurology
Amjad Khan, Anne Molitor, Sylvain Mayeur, Gaoqun Zhang, Bruno Rinaldi, Beatrice Lannes, Benoit Lhermitte, Muhammad Umair, Stefan T. Arold, Sylvie Friant, Sepand Rastegar, Mathieu Anheim, Seiamak Bahram, Raphael Carapito
Summary: A novel missense variant in the PPP1R1B gene was identified in a consanguineous family with generalized dystonia. The expression of PPP1R1B protein in movement control regions suggests its involvement in abnormal movements, making it a potential gene to be sequenced in patients with unexplained movement disorders.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Diane Doummar, Marco Treven, Leila Qebibo, David Devos, Jamal Ghoumid, Claudia Ravelli, Gottfried Kranz, Martin Krenn, Diane Demailly, Laura Cif, Jean-Baptiste Davion, Fritz Zimprich, Lydie Burglen, Michael Zech
Summary: The description of two unrelated patients expands the phenotype associated with CHD8 gene, presenting with childhood-onset progressive dystonia. These patients had overlapping phenotypes characterized by generalized dystonia and mild-to-moderate neurodevelopmental comorbidities. Deep brain stimulation led to clinical improvement in both cases, indicating CHD8 mutations can also result in dystonia-dominant phenotypes.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Julian E. Alecu, Afshin Saffari, Hellen Jumo, Marvin Ziegler, Oleksandr Strelko, Catherine A. Brownstein, Joseph Gonzalez-Heydrich, Lance H. Rodan, Mark P. Gorman, Mustafa Sahin, Darius Ebrahimi-Fakhari
Summary: CAPN1-associated hereditary spastic paraplegia (SPG76) is a rare and clinically heterogeneous syndrome caused by the loss of calpain-1 function. In this study, we present a translational approach to a case of an 18-year-old patient who initially showed psychiatric symptoms followed by spastic gait, intention tremor, and neurogenic bladder dysfunction, which are characteristic of a complex form of HSP. Genetic analysis revealed compound-heterozygous missense variants in CAPN1 and a previously reported heterozygous stop-gain variant in RCL1. In silico and in vitro functional studies confirmed the deleterious effect of the CAPN1 variants on calpain-1 activity and downstream signaling. These findings support the diagnosis of SPG76 and highlight the possibility of multiple gene involvement in complex neuropsychiatric diseases.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Clinical Neurology
Xiaoling Wu, Shaoping Zhong, Yang Cai, Yuling Yang, Yangye Lian, Jing Ding, Xin Wang
Summary: This study explores the association between the RELN gene and genetic generalized epilepsy (GGE). It identifies three novel pathogenic RELN variants that are potentially associated with GGE. These variants lead to relatively mild symptoms, possibly due to a loss-of-function mechanism.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2023)
Article
Clinical Neurology
Sarah E. Heron, Brigid M. Regan, Rebekah V. Harris, Alison E. Gardner, Matthew J. Coleman, Mark F. Bennett, Bronwyn E. Grinton, Katherine L. Helbig, Michael R. Sperling, Sheryl Haut, Eric B. Geller, Peter Widdess-Walsh, James T. Pelekanos, Melanie Bahlo, Slave Petrovski, Erin L. Heinzen, Michael S. Hildebrand, Mark A. Corbett, Ingrid E. Scheffer, Jozef Gecz, Samuel F. Berkovic
Summary: Missense variants in SLC32A1 have been identified as causative for GEFS+ and IGE, leading to altered neuronal inhibition by affecting GABA transport. These findings have been validated by studying multiple families.
Article
Clinical Neurology
Alessia Nasca, Niccolo E. Mencacci, Federica Invernizzi, Michael Zech, Ignacio J. Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe Bustos, Luigi M. Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J. Lubbe, Barbara Garavaglia, Daniele Ghezzi
Summary: Nasca et al. have discovered a new candidate gene for dystonia, ATP5F1B, which encodes a subunit of the mitochondrial ATP synthase. This gene is associated with early-onset isolated dystonia in two families with autosomal dominant inheritance and incomplete penetrance. Functional studies showed a dominant-negative effect of the identified ATP5F1B variants, leading to reduced activity of complex V and impaired mitochondrial function.
Article
Respiratory System
Maria Hollmen, Atte Laaka, Juulia J. Partanen, Jukka Koskela, Eva Sutinen, Riitta Kaarteenaho, Mari Ainola, Marjukka Myllarniemi
Summary: This study identified a potential genetic diagnostic marker, KIF15, for early-onset IPF. Variants in TERT and MUC5B also impact clinical course, while no distinct phenotypes were observed in patients with SPDL1 variants. Further research is needed to understand the biological mechanisms of KIF15 in IPF.
RESPIRATORY RESEARCH
(2023)
Article
Neurosciences
Ambreen Kanwal, Jose V. Pardo, Sadaf Naz
Summary: This study identified rare genetic variants that are highly likely to be the causes of extreme schizophrenia in two consanguineous families. These variants are very rare in public databases and absent in the control group. These findings suggest that some rare variants may play a role in the inheritance of psychosis or schizophrenia.
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Arian Ghanouni, Nikitha Jona, Hyder A. Jinnah, Gamze Kilic-Berkmen, Sandeep Shelly, Adam M. Klein
Summary: Adult-onset idiopathic laryngeal dystonia (LD) can spread to other muscles in the body. Patients with extralaryngeal onset dystonia can also exhibit spread to the larynx. This study aimed to identify demographic and clinical factors contributing to the spread of dystonia to and from the larynx.
Article
Cardiac & Cardiovascular Systems
Margherita Bigossi, Cyrielle Maroteau, Adem Y. Dawed, Alasdair Taylor, Sundararajan Srinivasan, Alaa' Lufti Melhem, Ewan R. Pearson, Roberto Pola, Colin N. A. Palmer, Moneeza K. Siddiqui
Summary: This study developed a clinically implementable gene risk score (GRS) based on four common variants in the SLCO1B1 gene to identify patients at risk of statin intolerance. The high-risk GRS was found to be associated with different phenotypes of statin intolerance, including statin-related myopathy and statin-related suspected rhabdomyolysis. Compared to using the Val174Ala genotype or recommended functional phenotypes, the GRS provided more reliable results. This study provides a simple and reliable genetic tool for estimating and predicting the risk of early-onset statin intolerance.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2023)
Article
Clinical Neurology
Ignacio J. Keller Sarmiento, Avram Fraint, Lisa Kinsley, Rizwan S. Akhtar, Vincenzo Silani, Steven J. Lubbe, Dimitri Krainc, Niccolo E. Mencacci
Summary: We report a case of young onset generalized dystonia with a previously unreported likely pathogenic THAP1 gene mutation, which was inherited from the unaffected father. Additionally, deep brain stimulation was found to have a positive effect on the cervical symptoms of dystonia.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Vasily Smirnov, Olivier Grunewald, Jean Muller, Christina Zeitz, Carolin D. Obermaier, Aurore Devos, Valerie Pelletier, Beatrice Bocquet, Camille Andrieu, Jean-Louis Bacquet, Elodie Lebredonchel, Saddek Mohand-Said, Sabine Defoort-Dhellemmes, Jose-Alain Sahel, Helene Dollfus, Xavier Zanlonghi, Isabelle Audo, Isabelle Meunier, Elise Boulanger-Scemama, Claire-Marie Dhaenens
Summary: Variants of the TTLL5 gene have been identified as a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). This study reports on five patients with biallelic variants of TTLL5, highlighting the importance of large deletions and suggesting that patients lacking variants in known genes may harbor CNVs to be discovered in TTLL5. Variable phenotypes in TTLL5-associated patients may be due to the presence of additional gene defects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Rick A. C. M. Boonen, Wouter W. Wiegant, Nandi Celosse, Bas Vroling, Stephan Heijl, Zsofia Kote-Jarai, Martina Mijuskovic, Simona Cristea, Nienke Solleveld-Westerink, Tom van Wezel, Niko Beerenwinkel, Rosalind Eeles, Peter Devilee, Maaike P. G. Vreeswijk, Giancarlo Marra, Haico van Attikum
Summary: This study describes a method using mouse embryonic stem cells to quantitatively determine the functional impact of 50 uncertain missense variants in the gene CHEK2. The results show that some missense variants impair protein function to a similar extent as truncating variants and are associated with an increased risk of breast cancer.
Review
Neurosciences
Chiara Reale, Federica Invernizzi, Celeste Panteghini, Barbara Garavaglia
Summary: This review provides an overview of how sex and gender affect disease development, emphasizing the importance of understanding gender differences in promoting personalized care. It highlights the role of genetic differences and clinical manifestations in neurological diseases such as Alzheimer's disease, Parkinson's disease, and obsessive-compulsive disorder.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Article
Clinical Neurology
Joanne Trinh, Theresa Luth, Susen Schaake, Bjorn-Hergen Laabs, Kathleen Schlueter, Joshua Lass, Jelena Pozojevic, Ronnie Tse, Inke Koenig, Roland Dominic Jamora, Raymond L. Rosales, Norbert Brueggemann, Gerard Saranza, Cid Czarina E. Diesta, Frank J. Kaiser, Christel Depienne, Christopher E. Pearson, Ana Westenberger, Christine Klein
Summary: By sequencing the genomes of XDP patients, researchers have discovered various mutations within the repetitive sequence SINE-VNTR-Alu(AGAGGG)(n), which may act as modifiers of disease expression in XDP.
Article
Genetics & Heredity
Anum Shafique, Beenish Arif, Mary Lynn Chu, Ellen Moran, Tooba Hussain, Francisca Millan Zamora, Elizabeth Wohler, Nara Sobreira, Christine Klein, Katja Lohmann, Sadaf Naz
Summary: This study investigated patients with dystonic or involuntary movement disorders in two families. Genetic analyses revealed mutations in the MRM2 gene that were associated with the phenotypes.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Clinical Neurology
Eva-Juliane Vollstedt, Susen Schaake, Katja Lohmann, Shalini Padmanabhan, Alexis Brice, Suzanne Lesage, Christelle Tesson, Marie Vidailhet, Isabel Wurster, Faycel Hentati, Anat Mirelman, Nir Giladi, Karen Marder, Cheryl Waters, Stanley Fahn, Meike Kasten, Norbert Bruggemann, Max Borsche, Tatiana Foroud, Eduardo Tolosa, Alicia Garrido, Grazia Annesi, Monica Gagliardi, Maria Bozi, Leonidas Stefanis, Joaquim J. Ferreira, Leonor Correia Guedes, Micol Avenali, Simona Petrucci, Lorraine Clark, Ekaterina Y. Fedotova, Natalya Y. Abramycheva, Victoria Alvarez, Manuel Menendez-Gonzalez, Silvia Jesus Maestre, Pilar Gomez-Garre, Pablo Mir, Andrea Carmine Belin, Caroline Ran, Chin-Hsien Lin, Ming-Che Kuo, David Crosiers, Zbigniew K. Wszolek, Owen A. Ross, Joseph Jankovic, Kenya Nishioka, Manabu Funayama, Jordi Clarimon, Caroline H. Williams-Gray, Marta Camacho, Mario Cornejo-Olivas, Luis Torres-Ramirez, Yih-Ru Wu, Guey-Jen Lee-Chen, Ana Morgadinho, Teeratorn Pulkes, Pichet Termsarasab, Daniela Berg, Gregor Kuhlenbaumer, Andrea A. Kuhn, Friederike Borngraeber, Giuseppe de Michele, Anna De Rosa, Alexander Zimprich, Andreas Puschmann, George D. Mellick, Jolanta Dorszewska, Jonathan Carr, Rosangela Ferese, Stefano Gambardella, Bruce Chase, Katerina Markopoulou, Wataru Satake, Tatsushi Toda, Malco Rossi, Marcelo Merello, Timothy Lynch, Diana A. Olszewska, Shen-Yang Lim, Azlina Ahmad-Annuar, Ai Huey Tan, Bashayer Al-Mubarak, Hasmet Hanagasi, Dariusz Koziorowski, Sibel Ertan, Gencer Genc, Patricia de Carvalho Aguiar, Melinda Barkhuizen, Marcia M. G. Pimentel, Rachel Saunders-Pullman, Bart van de Warrenburg, Susan Bressman, Mathias Toft, Silke Appel-Cresswell, Anthony E. Lang, Matej Skorvanek, Agnita J. W. Boon, Rejko Kruger, Esther M. Sammler, Vitor Tumas, Bao-Rong Zhang, Gaetan Garraux, Sun Ju Chung, Yun Joong Kim, Juliane Winkelmann, Carolyn M. Sue, Eng-King Tan, Joana Damasio, Peter Klivenyi, Vladimir S. Kostic, David Arkadir, Mika Martikainen, Vanderci Borges, Jens Michael Hertz, Laura Brighina, Mariana Spitz, Oksana Suchowersky, Olaf Riess, Parimal Das, Brit Mollenhauer, Emilia M. Gatto, Maria Skaalum Petersen, Nobutaka Hattori, Ruey-Meei Wu, Sergey N. Illarioshkin, Enza Maria Valente, Jan O. Aasly, Anna Aasly, Roy N. Alcalay, Avner Thaler, Matthew J. Farrer, Kathrin Brockmann, Jean-Christophe Corvol, Christine Klein
Summary: Through a worldwide online survey, we established an international cohort of individuals with PD-linked variants, providing harmonized and quality-controlled clinical and genetic data for each participant and promoting collaboration among researchers in the field of monogenic PD.
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Mirja Thomsen, Lara M. Lange, Christine Klein, Katja Lohmann
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Tatiana Usnich, Maria Olmedillas, Nathalie Schell, Jefri J. Paul, Filipa Curado, Snezana Skobalj, Ilona Csoti, Sibel Ertan, Doreen Gruber, Simone Zittel, Esther Sammler, Stuart H. Isaacson, Andrea A. Kuehn, David J. Pedrosa, Kathrin Reetz, Meike Kasten, Arndt Rolfs, Peter Bauer, Volha Skrahina, Christine Klein, Norbert Brueggemann
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Alfand Marl F. Dy Closas, Katja Lohmann, Ai Huey Tan, Norlinah Mohamed Ibrahim, Jia Lun Lim, Yi Wen Tay, Kalai Arasu Muthusamy, Azlina Binti Ahmad-Annuar, Christine Klein, Shen -Yang Lim
Summary: KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome that commonly progresses from the lower limbs to the upper limbs and eventually affects the craniocervical region. It is now recognized as one of the more common monogenic causes of dystonia syndromes. This report presents an atypical case of DYT-KMT2B with oromandibular dystonia as the initial symptom, which remained localized to this region for three decades. This is the first reported case of DYT-KMT2B from Southeast Asia and provides further evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.
JOURNAL OF MOVEMENT DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Melissa Vos, Christine Klein, Andrew A. Hicks
Summary: Sphingolipids, a subset of bioactive lipids, play a crucial role in proper neuronal function and are involved in almost all biological processes. Recent studies have found alterations in sphingolipids in patients with Parkinson's disease (PD), suggesting an important interaction between sphingolipids and PD-related cellular processes. This article discusses the role of sphingolipids in mitochondrial dysfunction, autophagy defects, and abnormal endosomal activity in PD.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Clinical Neurology
Miryam Carecchio, Michele Mainardi, Giulia Bonato
Summary: Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare neurodegenerative disease characterized by progressive bilateral calcification of the microvessels in the brain. The disease is caused by altered function of the Neurovascular Unit (NVU), leading to dysfunction of the blood-brain barrier and progressive neurodegeneration. Multiple genes have been identified as causative factors, and clinical presentation can vary from asymptomatic to movement disorders, cognitive decline, and psychiatric disturbances.
JOURNAL OF NEUROLOGY
(2023)
Editorial Material
Chemistry, Multidisciplinary
Nicola Marotta, Alessandro de Sire, Antonio Ammendolia
APPLIED SCIENCES-BASEL
(2023)
Article
Neurosciences
Maria Paulina Castelo Rueda, Alessandra Zanon, Valentina Gilmozzi, Alexandros A. Lavdas, Athina Raftopoulou, Sylvie Delcambre, Fabiola Del Greco, Christine Klein, Anne Gruenewald, Peter P. Pramstaller, Andrew A. Hicks, Irene Pichler
Summary: Homozygous or compound heterozygous variants in PRKN are causal for PD with highly penetrant symptom expression, while heterozygous variants may predispose to PD with reduced penetrance, through altered mitochondrial function. We generated lymphoblasts and hiPSC-derived neurons from non-manifesting heterozygous PRKN variant carriers and tested them for mitochondrial functionality. We identified molecular phenotypes that might be used to monitor heterozygous PRKN variant carriers during the prodromal phase and to test potential neuroprotective therapies.
NPJ PARKINSONS DISEASE
(2023)
Review
Medicine, General & Internal
Nicola Marotta, Alessandro de Sire, Dario Calafiore, Francesco Agostini, Lorenzo Lippi, Claudio Curci, Francesco Ferraro, Andrea Bernetti, Marco Invernizzi, Antonio Ammendolia
Summary: The COVID-19 pandemic has significantly impacted the surgical intervention and rehabilitation plan for ACL injuries. This scoping review examines the potential persistent symptoms and residual effects after COVID-19 disease, focusing on fatigue and neuromuscular disorders. Undertraining and knee muscular imbalance may lead to inefficient movement strategies, lack of knee stability, and increased load in ACL injuries. Telerehabilitation approaches have shown promise in maintaining strength and range of motion during the post-surgery period of COVID-19. However, further research is needed to determine the most effective interventions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Sport Sciences
Antonio Ammendolia, Alessandro de Sire, Lorenzo Lippi, Valerio Ammendolia, Riccardo Spano, Andrea Reggiani, Marco Invernizzi, Nicola Marotta
Summary: This study confirms the positive impact of cryo-ultrasound therapy combined with conventional physical therapy on the short-term recovery of elite football players with acute lateral ankle sprains, accelerating their rehabilitation and early return to sport. However, further research is needed to validate and optimize the long-term effects of this physical therapy modality.
Letter
Clinical Neurology
Luigi M. Romito, Valentina Leta, Barbara Garavaglia, Celeste Panteghini, Giovanna Zorzi, Antonio E. Elia, Fabiana Colucci, Miryam Carecchio, Roberto Eleopra
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Roxanne Lofredi, Ute Scheller, Aurika Mindermann, Lucia K. Feldmann, Joachim K. Krauss, Assel Saryyeva, Gerd-Helge Schneider, Andrea A. Kuehn
Summary: Pallidal deep brain stimulation (DBS) can alleviate symptoms in dystonia patients, but it may also cause movement slowness. This study found that after the cessation of pallidal stimulation, the movement speed of dystonia patients increased over time. The beta oscillations in the pallidum were found to be associated with the variance in movement speed.
MOVEMENT DISORDERS
(2023)