Skip Navigation
Skip to contents

JMD : Journal of Movement Disorders



Page Path
HOME > Search
3 "exome"
Article category
Publication year
Funded articles
Case Report
A New Phenotype of TUBB4A Mutation in a Family With Adult-Onset Progressive Spastic Paraplegia and Isolated Hypomyelination Leukodystrophy: A Case Report and Literature Review
Pei‐Chen Hsieh, Pei Shan Yu, Wen-Lang Fan, Chun‐Chieh Wang, Chih-Ying Chao, Yih‐Ru Wu
J Mov Disord. 2024;17(1):94-98.   Published online October 23, 2023
  • 1,007 View
  • 162 Download
AbstractAbstract PDFSupplementary Material
Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.
Brief communication
Utility of Clinical Exome Sequencing in Dystonia: A Single-Center Study From India
Vikram Venkappayya Holla, Koti Neeraja, Albert Stezin, Shweta Prasad, Bharat Kumar Surisetti, Manjunath Netravathi, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal
J Mov Disord. 2022;15(2):156-161.   Published online March 16, 2022
  • 2,749 View
  • 159 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary Material
With the use of next-generation sequencing in clinical practice, several genetic etiologies of dystonia have been identified. This study aimed to ascertain the utility of clinical exome sequencing (CES) in dystonia and factors suggestive of a genetic etiology.
This study was a retrospective chart review of patients with dystonia who had undergone CES for the evaluation of dystonia.
Forty-eight patients (35 males, 46 families) with dystonia were studied, with a mean age at onset of 16.0 ± 14.1 (1–58) years. A pathogenic/likely pathogenic variant was found in 20 patients (41.7%) among which 14 patients (29.2%) carried a novel variant. CES was more likely to detect a genetic diagnosis in patients with an early age at onset, i.e., ≤ 20 years.
CES is a useful tool in the diagnostic evaluation of dystonia, with a yield of close to 40%. Patients with an earlier age at onset have a higher likelihood of having dystonia due to a genetic cause than those with a later age at onset.


Citations to this article as recorded by  
  • Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights
    Burcu Atasu, Javier Simón-Sánchez, Hasmet Hanagasi, Basar Bilgic, Ann-Kathrin Hauser, Gamze Guven, Peter Heutink, Thomas Gasser, Ebba Lohmann
    Journal of Medical Genetics.2024; : jmg-2022-109099.     CrossRef
  • Whole exome sequencing and clinical investigation of young onset dystonia: What can we learn?
    Jong Hyeon Ahn, Ah Reum Kim, Woong-Yang Park, Jin Whan Cho, Jongkyu Park, Jinyoung Youn
    Parkinsonism & Related Disorders.2023; 115: 105814.     CrossRef
Case Report
PSEN1 p.Met233Val in a Complex Neurodegenerative Movement and Neuropsychiatric Disorder
Silke Appel-Cresswell, Ilaria Guella, Anna Lehman, Dean Foti, Matthew J. Farrer
J Mov Disord. 2018;11(1):45-48.   Published online January 11, 2018
  • 7,890 View
  • 178 Download
  • 12 Web of Science
  • 12 Crossref
AbstractAbstract PDF
Mutations in presenilin 1 (PSEN1) are the most common cause of autosomal dominant Alzheimer’s disease. Here, we report a Canadian-Vietnamese family carrying a PSEN1 p.Met233Val mutation with an exceptionally early and severe presentation that includes a wide range of atypical symptoms, including prominent ataxia, Parkinsonism, spasticity, dystonia, action tremor, myoclonus, bulbar symptoms, seizures, hallucinations and behavioral changes. Whole-exome sequencing (WES) was performed on the affected proband after many assessments over several years proved diagnostically inconclusive. The results were analyzed using the AnnEx “Annotated Exomes” browser (, a web-based platform that facilitates WES variant annotation and interpretation. High-throughput sequencing can be especially informative for complex neurological disorders, and WES warrants consideration as a first-line clinical test. Data analyses facilitated by web-based bioinformatics tools have great potential for novel insight, although confirmatory, diagnostically accredited Sanger sequencing is recommended prior to reporting.


Citations to this article as recorded by  
  • Presenilin Gene Mutation-associated Psychosis
    Mark A. Colijn, Zahinoor Ismail
    Alzheimer Disease & Associated Disorders.2024; 38(1): 101.     CrossRef
  • A heterozygous de novo PSEN1 mutation in a patient with early-onset parkinsonism
    Yueting Chen, Peng Liu, Fei Xie, Bo Wang, Zhiru Lin, Wei Luo
    Neurological Sciences.2022; 43(2): 1405.     CrossRef
  • Nomenclature of Genetic Movement Disorders: Recommendations of the International Parkinson and Movement Disorder Society Task Force – An Update
    Lara M. Lange, Paulina Gonzalez‐Latapi, Rajasumi Rajalingam, Marina A.J. Tijssen, Darius Ebrahimi‐Fakhari, Carolin Gabbert, Christos Ganos, Rhia Ghosh, Kishore R. Kumar, Anthony E. Lang, Malco Rossi, Sterre van der Veen, Bart van de Warrenburg, Tom Warner
    Movement Disorders.2022; 37(5): 905.     CrossRef
  • Progressive cognitive impairment and familial spastic paraparesis due to PRESENILIN 1 mutation: anatomoclinical characterization
    Miren Altuna, Rosa Larumbe, María Victoria Zelaya, Sira Moreno, Virginia García-Solaesa, Maite Mendioroz, María Antonia Ramos, María Elena Erro
    Journal of Neurology.2022; 269(9): 4853.     CrossRef
  • Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
    Jaya Bagaria, Eva Bagyinszky, Seong Soo A. An
    International Journal of Molecular Sciences.2022; 23(18): 10970.     CrossRef
  • Scoring Algorithm‐Based Genomic Testing in Dystonia: A Prospective Validation Study
    Michael Zech, Robert Jech, Sylvia Boesch, Matej Škorvánek, Ján Necpál, Jana Švantnerová, Matias Wagner, Ariane Sadr‐Nabavi, Felix Distelmaier, Martin Krenn, Tereza Serranová, Irena Rektorová, Petra Havránková, Alexandra Mosejová, Iva Příhodová, Jana Šarlá
    Movement Disorders.2021; 36(8): 1959.     CrossRef
  • PET/MRI Delivers Multimodal Brain Signature in Alzheimer’s Disease with De Novo PSEN1 Mutation
    Gayane Aghakhanyan, Dorothee Saur, Michael Rullmann, Christopher M. Weise, Matthias L. Schroeter, Ken Marek, Rami Abou Jamra, Solveig Tiepolt, Maria Strauss, Cordula Scherlach, Karl-Titus Hoffmann, Osama Sabri, Joseph Classen, Henryk Barthel
    Current Alzheimer Research.2021; 18(2): 178.     CrossRef
  • Spinocerebellar Ataxia-Like Presentation of the M233V PSEN1 Mutation
    Yury Seliverstov, Ilya Kanivets, Sergey Illarioshkin
    The Cerebellum.2020; 19(5): 744.     CrossRef
  • NetCore: a network propagation approach using node coreness
    Gal Barel, Ralf Herwig
    Nucleic Acids Research.2020; 48(17): e98.     CrossRef
  • Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer’s Disease with De Novo PSEN1 Mutation
    Jia Liu, Qianqian Wang, Donglai Jing, Ran Gao, Jing Zhang, Chunlei Cui, Hongwen Qiao, Zhigang Liang, Chaodong Wang, Pedro Rosa-Neto, Liyong Wu, Jianping Jia, Serge Gauthier
    Journal of Alzheimer's Disease.2019; 68(2): 551.     CrossRef
  • A Clinical Case of Patient Carrying Rare Pathological PSEN1 Gene Mutation (L424V) Demonstrates the Phenotypic Heterogenity of Early Onset Familial AD
    Kaloyan R. Stoychev, Maya Stoimenova-Popova, Petranka Chumpalova, Lilia Ilieva, Mohamed Swamad, Zornitsa Kamburova-Martinova
    Frontiers in Psychiatry.2019;[Epub]     CrossRef
  • Deficiency in the transcription factor NRF2 worsens inflammatory parameters in a mouse model with combined tauopathy and amyloidopathy
    Ana I. Rojo, Marta Pajares, Angel J. García-Yagüe, Izaskun Buendia, Fred Van Leuven, Masayuki Yamamoto, Manuela G. López, Antonio Cuadrado
    Redox Biology.2018; 18: 173.     CrossRef

JMD : Journal of Movement Disorders Twitter