Article
Clinical Neurology
Didem Tezen, Aysegul Gunduz, Meral Erdemir Kiziltan, Cengiz Yalcinkaya, Gunes Kiziltan
Summary: This report examines the case of a 5-year-old girl with early onset involuntary movements. The patient was found to have an ADCY5 gene mutation through whole exome sequencing. The study aims to contribute to a better understanding of the gene and the discovery of different treatment options.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Tatsuya Oishi, Conor S. Ryan, Rocio Vazquez Do Campo, Ruple S. Laughlin, Devon I. Rubin
Summary: Myokymic discharges can be present in a variety of neuromuscular conditions, with chronic median neuropathy being the most common in this cohort. Postradiation myokymia appears to have distinguishing morphological features compared with nonradiation cases when quantitatively analyzed.
Editorial Material
Clinical Neurology
Eduardo Benarroch
Summary: Emerging evidence suggests that different types of potassium channels play a significant role in shaping the electrophysiological properties of Purkinje cells, with potassium channel mutations being a recognized cause of SCAs and episodic ataxia. These findings point to potassium channels as potential therapeutic targets in these disorders.
Article
Biochemistry & Molecular Biology
Sebastian Dommel, Anne Hoffmann, Claudia Berger, Matthias Kern, Nora Kloting, Aimo Kannt, Matthias Blueher
Summary: The deletion of Adcy5 did not show expected physiological or biochemical benefits on adipose tissue, but allowed for independent study of its effects on AT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Clinical Neurology
Aaron S. Bower, Adeniyi Fisayo, Joachim M. Baehring, Bhaskar Roy
Summary: This case describes a rare occurrence of delayed radiation-induced myokymia with episodes of dysarthria and tongue fasciculations. The clinical presentation and electromyography findings were consistent with the diagnosis. While similar cases of radiation-induced dysarthria and tongue myokymia have been infrequently reported, this case also exhibited additional symptoms possibly related to ocular myokymia or neuromyotonia. Sodium channel inhibitors have shown some success in providing symptomatic relief.
Article
Genetics & Heredity
Garen Haryanyan, Ozkan Ozdemir, Kemal Tutkavul, Aysin Dervent, Semih Ayta, Cigdem Ozkara, Baris Salman, Emrah Yucesan, Yesim Kesim, Seda Susgun, Ugur Ozbek, Betul Baykan, Sibel A. Ugur Iseri, Nerses Bebek
Summary: Lafora disease is a severe form of progressive myoclonus epilepsy that is inherited in an autosomal recessive manner. It is associated with pathogenic variations in the EPM2A or NHLRC1 genes. The disease typically begins with seizures in adolescence and progresses to dementia, status epilepticus, and death within 10 years. Late-onset and slow progressing forms have also been reported, with some cases showing homozygosity for specific gene variants.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Multidisciplinary Sciences
Dirk Taenzler, Marc Kipping, Marcell Lederer, Wiebke Guenther, Christian Arlt, Stefan Huettelmaier, Andreas Merkenschlager, Andrea Sinz
Summary: We demonstrated the effects of caffeine, theophylline, and istradefylline on cAMP production by ADCY5-overexpressing cell lines. cAMP levels were compared between ADCY5 wild-type and R418W mutant cells. The purine derivatives reduced ADCY5-catalyzed cAMP production, with the R418W mutant cells showing the most significant reduction. In a case study, a slow-release formulation of theophylline showed better improvement in symptoms of ADCY5-related dyskinesia compared to previously administered caffeine. Theophylline could be considered as an alternative therapeutic option for treating ADCY5-related dyskinesia in patients.
Article
Clinical Neurology
Barbara Castellotti, Laura Canafoglia, Elena Freri, Maria Tappata, Giuliana Messina, Stefania Magri, Jacopo C. DiFrancesco, Martina Fanella, Carlo Di Bonaventura, Alessandra Morano, Tiziana Granata, Cinzia Gellera, Silvana Franceschetti, Roberto Michelucci
Summary: Variants of SEMA6B have been observed in an increasing number of patients with progressive myoclonus epilepsy (PME) and developmental encephalopathy, sometimes accompanied by epilepsy. Most commonly, these variants affect exon 17 and result in the production of abnormal proteins with toxic gain of function. This study reports on three patients with de novo truncating SEMA6B variants in exon 17, who presented with PME, developmental delay, motor and cognitive impairment, worsening myoclonus, and various types of epilepsy. The findings suggest that developmental delay should be considered as part of the PME plus developmental delay category. The study contributes to our understanding of SEMA6B variants associated with PMEs, but further research is needed to clarify the correlation between phenotypic features and variant type or location.
Review
Clinical Neurology
Felipe Vial, Shabbir Hussain I. Merchant, Patrick McGurrin, Mark Hallett
Summary: Diagnosing and characterizing myoclonus can be challenging, and electrophysiology is crucial to complement clinical findings and localize the source of the movement. This article serves as a practical manual on conducting a myoclonus study, providing detailed descriptions of various recording techniques and analysis considerations. The authors also discuss factors hindering the broader use of these techniques.
JOURNAL OF CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Genetics & Heredity
Jie Li, Chenglong Shen, Kaijuan Zhang, Zhihan Niu, Zhengqing Liu, Shaoli Zhang, Yongsheng Wang, Xianyong Lan
Summary: This study identified three novel indel mutations of the bovine ADCY5 gene, two of which were significantly correlated with ovarian phenotypic traits or corpus luteum or albicans traits. These findings contribute to improving female fertility in cattle through the application of molecular marker-assisted selection (MAS), which can accelerate the development of the cattle industry.
Article
Pediatrics
Mohammed F. Aljabri, Naglaa M. Kamal, Abdulrhman Alghamdi, Hamdan Alghamdi, Naif Alomairi
Summary: This report presents a case of myoclonus dystonia in a twenty-month-old Saudi boy with a pathogenic mutation in the sarcoglycan gene, which showed significant response to carbamazepine therapy and maintained the effect during a 4-year follow-up. The findings suggest a potential therapeutic option for SGCE mutations with carbamazepine.
ITALIAN JOURNAL OF PEDIATRICS
(2021)
Article
Genetics & Heredity
Dana Marafi, Nina Kozar, Ruizhi Duan, Stephen Bradley, Kenji Yokochi, Fuad Al Mutairi, Nebal Waill Saadi, Sandra Whalen, Theresa Brunet, Urania Kotzaeridou, Daniela Choukair, Boris Keren, Caroline Nava, Mitsuhiro Kato, Hiroshi Arai, Tawfiq Froukh, Eissa Ali Faqeih, Ali M. AlAsmari, Mohammed M. Saleh, Filippo Pinto E. Vairo, Pavel N. Pichurin, Eric W. Klee, Christopher T. Schmitz, Christopher M. Grochowski, Tadahiro Mitani, Isabella Herman, Daniel G. Calame, Jawid M. Fatih, Haowei Du, Zeynep Coban-Akdemir, Davut Pehlivan, Shalini N. Jhangiani, Richard A. Gibbs, Satoko Miyatake, Naomichi Matsumoto, Laura J. Wagstaff, Jennifer E. Posey, James R. Lupski, Dies Meijer, Matias Wagner
Summary: The LGI family of genes, including LGI1-4, are highly expressed in the nervous systems of mammals. Variations in LGI1 and LGI4 are associated with neurological disorders, while no diseases have been reported to be associated with LGI2 or LGI3. This study identified individuals with deleterious variants in LGI3 and found that these variants cause a clinically recognizable PNHS trait characterized by developmental delay and intellectual disability.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Dermatology
Sharmeen Chagani, Mariana P. De Macedo, Fernando Carapeto, Feng Wang, Diego M. Marzese, Khalida Wani, Lauren E. Haydu, Weiyi Peng, Giang T. Ong, Sarah E. Warren, Joseph M. Beechem, Dave S. B. Hoon, Gordon B. Mills, Michael T. Tetzlaff, Alexander J. Lazar, Lawrence N. Kwong, Michael A. Davies
Summary: Loss of PTEN protein expression in melanoma is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune and targeted therapies.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Clinical Neurology
Aurelie Meneret, Shekeeb S. Mohammad, Laura Cif, Diane Doummar, Claudio DeGusmao, Mathieu Anheim, Magalie Barth, Philippe Damier, Nathalie Demonceau, Jennifer Friedman, Cecile Gallea, Domitille Gras, Juliana Gurgel-Giannetti, Emily A. Innes, Jan Necpal, Florence Riant, Sandrine Sagnes, Catherine Sarret, Yury Seliverstov, Vijayashankar Paramanandam, Kuldeep Shetty, Christine Tranchant, Mohamed Doulazmi, Marie Vidailhet, Tamara Pringsheim, Emmanuel Roze
Summary: A retrospective study found that caffeine is effective in improving symptoms of ADCY5-related dyskinesia and should be considered as a first-line treatment option with good tolerability.
MOVEMENT DISORDERS
(2022)
Article
Genetics & Heredity
Peter Sparber, Igor Bychkov, Denis Pyankov, Mikhail Skoblov
Summary: Dravet syndrome is a severe form of epilepsy characterized by early onset seizures, developmental regression, ataxia, and motor deficits. Most patients with Dravet syndrome have loss-of-function pathogenic variants in the SCN1A gene, but some patients still cannot be diagnosed even after comprehensive genetic testing. This study developed a splicing reporter assay to analyze the effects of poison exons in the SCN1A gene, and showed the potential of using antisense-modified uridine-rich U7 small nuclear RNAs as a therapeutic intervention for deep-intronic variants in Dravet syndrome.
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.
Letter
Genetics & Heredity
Salem Alawbathani, Suliman Khan, Ana Westenberger, Christian Beetz, Lokesh Lingappa
Article
Biochemistry & Molecular Biology
Roberta Biasiotto, Maria Koesters, Katharina Tschigg, Peter P. Pramstaller, Norbert Brueggemann, Max Borsche, Christine Klein, Andrew A. Hicks, Deborah Mascalzoni
Summary: Recall-by-genotype (RbG) research involves recalling participants based on their genotype, potentially leading to disclosure of unwanted genetic information. A study on participant views and preferences regarding RbG research approach provides valuable insights for RbG policy development.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Clinical Neurology
Max Borsche, Andre Maertens, Philipp Hoermann, Theresa Brueckmann, Katja Lohmann, Sinem Tunc, Christine Klein, Karsten Hiller, Alexander Balck
Summary: This study investigates the differences in glucose metabolism between Parkinson's disease (PD) patients and healthy controls using advanced biochemical methods. The results show that glucose production pathways differ between idiopathic and PRKN mutation carriers, and are associated with diabetes. This study provides the first in vivo evidence for alterations in glucose metabolism in idiopathic PD.
MOVEMENT DISORDERS
(2023)
Review
Clinical Neurology
Malco Rossi, Moath Hamed, Jon Rodriguez-Antiguedad, Mario Cornejo-Olivas, Marianthi Breza, Katja Lohmann, Christine Klein, Rajasumi Rajalingam, Connie Marras, Bart P. van de Warrenburg
Summary: This article systematically reviewed the genotype-phenotype relationships and reevaluated the pathological range of repeat expansions in ATX-TBP. The study proposed new cutoff values for reduced penetrance (41-45 expanded repeats) and full penetrance (46-66 expanded repeats), which have important diagnostic and counseling implications and may guide future clinical trial protocols.
MOVEMENT DISORDERS
(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
Clinical Neurology
Alonso Zea Vera, Adrienne Bruce, Travis R. Larsh, Zachary Jordan, Norbert Bruggemann, Ana Westenberger, Alberto J. Espay, Donald L. Gilbert, Steve W. Wu
Summary: POLR3A-related disorders exhibit significant phenotypic pleomorphism, including a range of movement disorders such as parkinsonism, dystonia, ataxia, and spasticity. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Letter
Clinical Neurology
Max Borsche, Neringa Pratuseviciute, Susen Schaake, Frauke Hinrichs, Gabriel Morel, Jan Uter, Katja Lohmann, Christine Klein, Dario R. Alessi, Johann Hagenah, Esther Sammler
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Paula Saffie Awad, Katja Lohmann, Yasmin Hirmas, Frauke Hinrichs, Mirja Thomsen, Marcelo Kauffman, Theresa Lueth, Joanne Trinh, Ana Westenberger, Pedro Chana-Cuevas, Christine Klein
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Sebastian Loens, Feline Hamami, Katja Lohmann, Thorsten Odorfer, Chi Wang Ip, Simone Zittel, Kirsten E. Zeuner, Judith Everding, Jos Becktepe, Katrin Marth, Friederike Borngraeber, Katja Kollewe, Christoph Kamm, Andrea A. Kuehn, Mathias Gelderblom, Jens Volkmann, Christine Klein, Tobias Baeumer
Summary: This study aims to identify clinical and demographic features associated with heritability of yet idiopathic dystonia. Tremor is associated with an increased risk of familial clustering of dystonia and with a family history of tremor itself. This indicates a hereditable dystonia-tremor syndrome with a clinical spectrum ranging from tremor-predominant diseases to dystonia.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Cell & Tissue Engineering
Axel Chemla, Giuseppe Arena, Claudia Saraiva, Clara Berenguer-Escuder, Dajana Grossmann, Anne Grunewald, Christine Klein, Philip Seibler, Jens C. Schwamborn, Rejko Kruger
Summary: In this study, two Parkinson's disease patients' primary skin fibroblasts carrying distinct heterozygous mutations in the RHOT1 gene encoding Miro1 were reprogrammed into induced pluripotent stem cells (iPSCs) using episomal reprogramming. Isogenic gene-corrected lines were generated using CRISPR/Cas9 technology. Both isogenic pairs were comprehensively characterized and quality assured to study the Miro1-related molecular mechanisms underlying neurodegeneration in iPSC-derived neuronal models.
STEM CELL RESEARCH
(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)
Article
Clinical Neurology
Jun-Pyo Hong, Hanim Kwon, Euyhyun Park, Sun-Uk Lee, Chan-Nyoung Lee, Byung-Jo Kim, Ji-Soo Kim, Kun-Woo Park
Summary: In patients with mild-to-moderate PD, vestibular function assessed by video head-impulse tests appears relatively preserved and has minimal impact on the risk of falls. Risk of postural instability is associated with the severity of clinical symptoms in PD.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yaqin Xiang, XiuRong Huang, Qian Xu, Zhenhua Liu, Yase Chen, Qiying Sun, Junling Wang, Hong Jiang, Lu Shen, Xinxiang Yan, Beisha Tang, Jifeng Guo
Summary: Using the novel data-driven method DEBM, this study determined the sequence of several common biomarker changes in Parkinson's disease (PD). The left putamen was found to be the earliest biomarker to become abnormal, followed by the right putamen, CSF alpha-synuclein, right caudate, left caudate, and serum NfL. The estimated disease stages showed significant differences between PD and healthy controls, and achieved a high accuracy for distinguishing PD from HC.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yan Li, David J. McLernon, Carl E. Counsell, Angus D. Macleod
Summary: This study aimed to investigate the incidence and risk factors for institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). The study found that institutionalisation was more frequent in AP compared to PD and controls. Age, poorer cognition, and more-severe parkinsonian impairment were independent predictors of institutionalisation.
PARKINSONISM & RELATED DISORDERS
(2024)
