Review
Clinical Neurology
Jochen Schaefer, Annika Saak, Carsten G. Bonnemann, Sandra Jackson
Summary: Tremor is a common neurological symptom with various potential causes, most commonly linked to pacemakers in the central nervous system. Myogenic tremor, a recently discovered type of tremor believed to originate in muscle itself, presents as a high frequency, postural, and kinetic tremor. The tremor is thought to be generated in the sarcomere and may be a valuable clinical tool for differentiating myopathies.
CURRENT OPINION IN NEUROLOGY
(2021)
Article
Clinical Neurology
Jos S. Becktepe, Johannes Busse, Ulf Jensen-Kondering, Inken Toedt, Stephan Wolff, Kirsten E. Zeuner, Daniela Berg, Oliver Granert, Guenther Deuschl
Summary: The study found a significant positive correlation between white matter hyperintensity (WMH) volume and tremor severity, as well as a significant negative correlation with the mean accelerometric tremor frequency. The total WMH volume predicted tremor severity, while age and disease duration were not significant in our multiple linear regression model.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Saki Uneoka, Tomoko Kobayashi, Yurika Numata-Uematsu, Yoshitsugu Oikawa, Yu Katata, Yukimune Okubo, Yu Abe, Atsuo Kikuchi, Jun Takayama, Gen Tamiya, Shigeo Kure, Kayoko Saito, Mitsugu Uematsu
Summary: MYBPC1 mutations exhibit clinical features similar to spinal muscular atrophy (SMA), including hypotonia, involuntary movement of the tongue and limbs, and delayed motor development. Differentiating SMA from other diseases is crucial for the development of novel therapies for early childhood.
PEDIATRIC NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Ravi Kumar Dutta, Malin Larsson, Thomas Arnesen, Anette Heie, Martin Walz, Piero Alesina, Oliver Gimm, Peter Soderkvist
Summary: This study identified a susceptibility locus on chromosome Xq13.3 associated with APAs using a GWAS approach. Direct genotyping of a sentinel SNP in a replication cohort showed strong significance, and sequencing of an adjacent gene revealed a rare variant. Investigation of expression quantitative trait loci provided insights into the genetic basis and potential novel mechanistic explanations for the association of the SNPs with APAs.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Nilufer Bal, Yildizhan Sengul, Meliha Basoz Behmen, Allison Powell, Elan D. Louis
Summary: This study used cVEMP and oVEMP tests to investigate the vestibulocollic and vestibuloocular reflex arcs and evaluate cerebellar and brainstem involvement in ET. The ET group showed higher pathological responses in oVEMP compared to the control group, suggesting that upper brainstem pathways may be more affected by ET.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Neurosciences
Jeyeon Lee, Jiwon Kim, Joshua Cortez, Su-Youne Chang
Summary: By using a rat HA-induced tremor model, this study investigated the electrophysiological response of the motor circuit, including the vlTh and M1, and the modulatory effect of thalamic DBS. The results showed that theta and HFO band powers significantly increased in both vlTh and M1 after HA administration, and this activity was modulated by propranolol and thalamic DBS. Theta band phase synchronization between vlTh and M1 was enhanced during HA-induced tremor, and the cross-frequency coupling in vlTh was associated with the state of HA-induced tremor.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Yun Soo Hong, Stephanie L. Battle, Wen Shi, Daniela Puiu, Vamsee Pillalamarri, Jiaqi Xie, Nathan Pankratz, Nicole J. Lake, Monkol Lek, Jerome I. Rotter, Stephen S. Rich, Charles Kooperberg, Alex P. Reiner, Paul L. Auer, Nancy Heard-Costa, Chunyu Liu, Meng Lai, Joanne M. Murabito, Daniel Levy, Megan L. Grove, Alvaro Alonso, Richard Gibbs, Shannon Dugan-Perez, Lukasz P. Gondek, Eliseo Guallar, Dan E. Arking
Summary: Based on the study of participants in the UK Biobank, it was found that mitochondrial heteroplasmy is associated with increased risk of all-cause mortality and the prevalence and incidence of cancer, especially leukemia.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Hongling Fu, Qiu Wang, Hanmin Liu
Summary: PMLD is a serious hypomyelinating leukodystrophy that affects children's quality of life and can result from mutations in different genes. Early genetic counseling is suggested for accurate diagnosis and treatment.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2021)
Article
Respiratory System
Aabida Saferali, Dandi Qiao, Wonji Kim, Karen Raraigh, Hara Levy, Alejandro A. Diaz, Garry R. Cutting, Michael H. Cho, Craig P. Hersh
Summary: This study found that smokers who carry one deleterious CFTR variant have higher rates of chronic bronchitis, while presence of two CFTR variants may be associated with COPD. These results indicate that genetically mediated reduction in CFTR function contributes to COPD related phenotypes, in particular chronic bronchitis.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Enrico Bugiardini, Andreia M. Nunes, Ariany Oliveira-Santos, Marisela Dagda, Tatiana M. Fontelonga, Pamela Barraza-Flores, Alan M. Pittman, Jasper M. Morrow, Matthew Parton, Henry Houlden, Perry M. Elliott, Petros Syrris, Roderick P. Maas, Mohammed M. Akhtar, Benno Kusters, Joost Raaphorst, Meyke Schouten, Erik-Jan Kamsteeg, Baziel van Engelen, Michael G. Hanna, Rahul Phadke, Luis R. Lopes, Emma Matthews, Dean J. Burkin
Summary: This study describes the pathological changes caused by ITGA7 mutations in skeletal and cardiac muscle. Patients exhibited cardiac dysfunction and respiratory insufficiency, and mouse experiments also showed abnormalities related to the heart and muscles. The results suggest a critical role for integrin alpha 7 beta 1 in cardiac function.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Multidisciplinary Sciences
Hideo Shimizu, Hirohiko Hohjoh
Summary: This study reveals that FMR1, FXR1, and Dlg4 genes associated with Fragile X syndrome are involved in the regulation of UPS activity and affect neurite outgrowth.
SCIENTIFIC REPORTS
(2023)
Article
Hematology
Sarah Gooding, Naser Ansari-Pour, Fadi Towfic, Maria Ortiz Estevez, Philip P. Chamberlain, Kao-Tai Tsai, Erin Flynt, Marissa Hirst, Dan Rozelle, Paula Dhiman, Paola Neri, Karthik Ramasamy, Nizar Bahlis, Paresh Vyas, Anjan Thakurta
Summary: The study found that in patients with myeloma, as the exposure to IMiD drugs increased, the frequency of CRBN abnormalities also increased gradually, with almost one-third of patients having CRBN alterations by the time they were refractory to pomalidomide (POM). These CRBN abnormalities were associated with inferior outcomes to POM in patients already refractory to lenalidomide (LEN).
Article
Physiology
Caroline Michele Marinho Marciano, Adriana Mercia Guaratini Ibelli, Jorge Augusto Petroli Marchesi, Jane de Oliveira Peixoto, Lana Teixeira Fernandes, Igor Ricardo Savoldi, Kamilla Bleil do Carmo, Monica Correa Ledur
Summary: Studies have shown that disruption of muscle and calcium signaling pathways may be triggering White Striping in chickens. Improving our understanding of the genetic basis involved in this myopathy could help reduce its prevalence in poultry production.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Janelle Geist Hauserman, Janis Stavusis, Humberto C. Joca, Joel C. Robinett, Laurin Hanft, Jack Vandermeulen, Runchen Zhao, Joseph P. Stains, Konstantinos Konstantopoulos, Kerry S. McDonald, Christopher Ward, Aikaterini Kontrogianni-Konstantopoulos
Summary: The E248K pathogenic variant in myosin binding protein-C results in a mouse model that faithfully recapitulates the symptoms of generalized myopathy, tremors, and skeletal deformities seen in human carriers. Biochemical and ultrastructural assessments show that the loss-of-function phenotype in mutant muscles is primarily driven by disordered and misaligned sarcomeres containing fragmented internal membranes.
Article
Biochemistry & Molecular Biology
Giulia Barcia, Marlene Rio, Zahra Assouline, Coralie Zangarelli, Charles-Joris Roux, Pascale de Lonlay, Julie Steffann, Isabelle Desguerre, Arnold Munnich, Jean-Paul Bonnefont, Nathalie Boddaert, Agnes Rotig, Metodi D. Metodiev, Benedetta Ruzzenente
Summary: Mitochondrial translation is crucial for the synthesis of ATP in the body. Variants in both mitochondrial DNA and nuclear genes encoding mitochondrial translation factors can lead to mitochondrial diseases. Mutations in the FARS2 gene are linked to conditions like spastic tetraparesis and myoclonic epilepsy.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Ieva Micule, Baiba Lace, Nathan T. Wright, Nicolas Chrestian, Jurgis Strautmanis, Mikus Diriks, Janis Stavusis, Dita Kidere, Elfa Kleina, Anna Zdanovica, Nataly Laflamme, Nadie Rioux, Samarth Thonta Setty, Sander Pajusalu, Arnaud Droit, Monkol Lek, Serge Rivest, Inna Inashkina
Summary: Variants in the HPDL gene have been associated with a hereditary neurological disease with a wide range of clinical severities. Two probands from unrelated families with different clinical courses were found to have homozygous variants in the HPDL gene, despite no known parental consanguinity. Reductions in citrate synthase and mitochondrial complex I activity in different tissues of both probands suggest a mitochondrial nature in the pathogenesis associated with HPDL mutations.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Baiba Lace, Sander Pajusalu, Diana Livcane, Ieva Grinfelde, Ilze Akota, Ieva Maulina, Biruta Barkane, Janis Stavusis, Inna Inashkina
Summary: Craniofacial morphogenesis is a complex process that can be affected by genetic and environmental factors, leading to orofacial clefts. A study using whole genome sequencing found rare disease variants in genes associated with isolated cleft palate in 17% of patients. These findings suggest that newborns with orofacial clefts should be offered genetic testing, especially for known cleft lip and palate genes.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Baiba Lace, Ieva Micule, Viktorija Kenina, Signe Setlere, Jurgis Strautmanis, Inese Kazaine, Gita Taurina, Daiga Murmane, Ieva Grinfelde, Liene Kornejeva, Zita Krumina, Olga Sterna, Ilze Radovica-Spalvina, Inta Vasiljeva, Linda Gailite, Janis Stavusis, Diana Livcane, Dita Kidere, Ieva Malniece, Inna Inashkina
Summary: This study evaluated the effectiveness of genetic analysis as a first-tier test for NMD patients and calculated the disease prevalence and allelic frequencies of recurrent genetic variants. The results showed that spinal muscular atrophy and dystrophinopathies were the most common childhood-onset NMDs in Latvia, while congenital myotonia was the most frequent NMD in the population.
NEUROLOGY-GENETICS
(2022)
Article
Genetics & Heredity
Magdalena Mroczek, Inna Inashkina, Janis Stavusis, Pawel Zayakin, Andrey Khrunin, Ieva Micule, Victorija Kenina, Anna Zdanovica, Jana Zidkova, Lenka Fajkusova, Svetlana Limborska, Anneke J. van der Kooi, Esther Brusse, Lea Leonardis, Ales Maver, Sander Pajusalu, Katrin Ounap, Sanna Puusepp, Paula Dobosz, Mateusz Sypniewski, Birute Burnyte, Baiba Lace
Summary: Research indicates the presence of the investigated intronic CAPN3 variant NM_000070.3:c.1746-20C>G in Central and Eastern Europe with a frequency exceeding 1%, with conflicting interpretations on its pathogenicity. Data collected on 14 patients carrying the CAPN3 c.1746-20C>G variant in conjunction with another CAPN3 pathogenic/likely pathogenic variant reveals a consistent phenotype of mild to moderate severity calpainopathy. The variant is most commonly found in the North/West regions of Russia and may have originated from there. Molecular studies demonstrate the production of different splicing isoforms in the muscle. It is hypothesized that c.1746-20C>G is a hypomorphic variant that leads to a reduction in RNA and protein expression, with only individuals exhibiting a higher ratio of abnormal isoforms being affected. Reclassifying the CAPN3 variant c.1746-20C>G from a variant with conflicting interpretations on pathogenicity to a hypomorphic variant explains numerous unidentified cases of limb girdle muscular dystrophy R1 calpain 3-related in Eastern and Central Europe.
Article
Biochemistry & Molecular Biology
Gianna E. Mauriello, Grace E. Moncure, Roujon A. Nowzari, Callie J. Miller, Nathan T. Wright
Summary: In this study, the researchers investigated the structure and flexibility of the N-terminal region of the giant cytoskeletal protein obscurin using NMR, SAXS, and MD techniques. They found that longer linkers in this region are associated with higher interdomain flexibility and result in a moderately compact multidomain structure. They also identified a "sweet spot" linker length of 5 residues that leads to extended dual-domain systems, while longer or shorter linkers result in less extended structures. Mathematical modeling suggested that domains 1-18 can form tangles if left alone in solution. This study provides important insights into the structure and function of obscurin.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Neurosciences
Daniel B. Free, Ian Syndergaard, Adam C. Pigg, Silvia Muceli, Johanna Thompson-Westra, Karin Mente, Carine W. Maurer, Dietrich Haubenberger, Mark Hallett, Dario Farina, Steven K. Charles
Summary: Although there are limited treatment options for essential tremor (ET), peripheral tremor suppression methods have shown potential. This study aimed to quantify the relationships between tremor activity in muscles throughout the upper limb. Muscle activity was recorded from 15 major upper limb muscles in subjects with ET, and coherence and phase difference between muscle pairs were calculated. The results showed that patients had significantly more coherence than control subjects, particularly among agonists.
JOURNAL OF NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
Felipe Vial, Patrick McGurrin, Thomas Osterholt, Debra J. Ehrlich, Susan T. Iannacone, Sandra Donkervoort, Sarah B. Neuhaus, Katherine C. Chao, Carsten G. Bonnemann, Dietrich Haubenberger, Mark Hallett
Summary: This study reports the first case of an individual with tremor found to have a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7) gene. Through a detailed electrophysiological characterization of the tremor syndrome in this individual with a myopathy and MYH7 variant, the phenotypic spectrum and pathomechanism of myogenic tremors in skeletal sarcomeric myopathies are further elucidated. The results suggest that the tremor may originate at the sarcomere level within muscles and is picked up by muscle spindles, leading to activating input to the neuraxis segment. Additionally, the stability of the tremor frequency indicates the presence of central oscillators at the segmental level.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Letter
Clinical Neurology
Nahid Olfati, Dennis W. Dickson, Ali Shoeibi, Dietrich Haubenberger, Irene Litvan
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Genetics & Heredity
L. Mauring, S. Puusepp, M. Parik, E. Roomets, R. Teek, T. Reimand, S. Pajusalu, K. Kaljurand, K. Ounap
Summary: In this study, a new autosomal recessive inheritance pattern of Leber's hereditary optic neuropathy (LHON) caused by a missense variant in the DNAJC30 gene was described. The c.152A > G, p.(Tyr51Cys) variant was found to be the most common in patients from Eastern Europe and is believed to be a founder variant. The study reported the first two cases of DNAJC30-linked autosomal recessive LHON in Estonia, with severe loss of central vision and clinical features indistinguishable from mitochondrial LHON.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Clinical Neurology
Norman Ilves, Sander Pajusalu, Tiina Kahre, Rael Laugesaar, Ustina Samarina, Dagmar Loorits, Pille Kool, Pilvi Ilves
Summary: This study aimed to evaluate genetic risk factors in term-born and preterm infants with periventricular hemorrhagic infarction (PVHI) and periventricular venous infarction (PVVI). The results showed that pathogenic variants in COL4A1/A2 and COL5A1 genes were commonly found in children with PVHI/PVVI, suggesting that genetic testing should be considered for all children with PVHI/PVVI, with a focus on COL4A1/A2 and COL5A1 genes.
JOURNAL OF CHILD NEUROLOGY
(2023)
Article
Clinical Neurology
Erin Furr Stimming, Daniel Claassen, Elise Kayson, Jody Goldstein, Raja Mehanna, Hui Zhang, Grace S. Liang, Dietrich Haubenberger
Summary: Valbenazine was evaluated as a treatment for chorea associated with Huntington's disease, and it was found to be more effective than placebo in improving chorea symptoms and well tolerated.
Article
Medicine, Research & Experimental
Sally C. Fletcher, Charlotte Hall, Tristan J. Kennedy, Sander Pajusalu, Monica H. Wojcik, Uncaar Boora, Chan Li, Kaisa Teele Oja, Eline Hendrix, Christian A. E. Westrip, Regina Andrijes, Sonia K. Piasecka, Mansi Singh, Mohammed E. El-Asrag, Anetta Ptasinska, Vallo Tillmann, Martin R. Higgs, Deanna A. Carere, Andrew D. Beggs, John Pappas, Rachel Rabin, Stephen J. Smerdon, Grant S. Stewart, Katrin Ounap, Mathew L. Coleman
Summary: Although protein hydroxylation is not well understood, recent research has revealed its role in oxygen sensing and hypoxia biology. JMJD5, a protein hydroxylase essential for mouse embryonic development and viability, has been found to have pathogenic variants that cause severe developmental disorders in humans. These variants affect mRNA splicing, protein stability, and hydroxylase activity, leading to failure to thrive, intellectual disability, and facial dysmorphism. This study contributes to our understanding of the importance of protein hydroxylases in human development and disease.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Dita Kidere, Pawel Zayakin, Diana Livcane, Marina Makrecka-Kuka, Janis Stavusis, Baiba Lace, Tsu-Kung Lin, Chia-Wei Liou, Inna Inashkina
Summary: Mitochondria play essential roles in diverse cellular functions, such as ATP synthesis and regulation of nuclear gene expression. Leigh syndrome is a neurological disorder caused by complex I deficiency, leading to impaired mitochondrial energy production. The mtDNA variant m.13513G>A has been associated with Leigh syndrome. This study examined the impact of this mtDNA variant on the OXPHOS system and cell retrograde signaling. The results showed that increasing levels of the variant were associated with reduced OXPHOS system activity and complex I defect, as well as profound changes in nuclear gene expression.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)