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ε-Sarcoglycan: Unraveling the Myoclonus-Dystonia Gene

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Abstract

Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder, with an estimated prevalence of about 2 per 1,000,.000 in Europe, characterized by myoclonic jerks in combination with focal or segmental dystonia. Pathogenic variants in the gene encoding ε-sarcoglycan (SGCE), a maternally imprinted gene, are the most frequent genetic cause of MD. To date, the exact role of ε-sarcoglycan and the pathogenic mechanisms that lead to MD are still unknown. However, there are more than 40 reported isoforms of human ε-sarcoglycan, pointing to a complex biology of this protein. Additionally, some of these are brain-specific isoforms, which may suggest an important role within the central nervous system. In the present review, we aim to provide an overview of the current state of knowledge of ε-sarcoglycan. We will focus on the genetic landscape of SGCE and the presence and plausible role of ε-sarcoglycan in the brain. Finally, we discuss the importance of the brain-specific isoforms and hypothesize that SGCE may play essential roles in normal synaptic functioning and their alteration will be strongly related to MD.

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Acknowledgements

This work was supported by a Grant from Myoclonus Dystonia Syndrome Spanish association (ALUDME) (grant PIC/124/16), grant PI18/01319 from the Plan Nacional de I +D + I, award AC17/00005 by the Carlos III Health Institute (ISCIII) through AES2017 and within the NEURON framework, Career Integration Grant (ref. 304111), Ramón y Cajal Fellowship (RYC-2011-08391p), IEDI-2017-00822 by the Spanish Ministry of Economy and Competitiveness, and Agency for Management of University and Research Grants (AGAUR) (SGR14-297 and 2017 SGR 1776).

Funding

This work was supported by a Grant from Myoclonus Dystonia Syndrome Spanish association (ALUDME) (grant PIC/124/16) and grant PI18/01319 from the Plan Nacional de I +D + I.

AB. financial support was provided by: Award AC17/00005 by ISCIII through AES2017 and within the NEURON framework, Career Integration Grant (ref. 304111), Ramón y Cajal Fellowship (RYC-2011-08391p), IEDI-2017-00822, and AGAUR (SGR14-297 and 2017 SGR 1776).

Author information

Authors and Affiliations

  1. Paediatric Neurology Research Group, Hospital Vall d’Hebrón, Universitat Autònoma de Barcelona, Vall d’Hebrón Research Institute, Barcelona, Spain

    Ana Cazurro-Gutiérrez, Anna Marcé-Grau, Marta Correa-Vela, Ainara Salazar, María I. Vanegas, Alfons Macaya & Belén Pérez-Dueñas

  2. Universitat Autònoma de Barcelona, Barcelona, Spain

    Ana Cazurro-Gutiérrez, Marta Correa-Vela, Alfons Macaya, Àlex Bayés & Belén Pérez-Dueñas

  3. Paediatric Neurology Department, Hospital Vall d’Hebron, Barcelona, Spain

    Ainara Salazar, Alfons Macaya & Belén Pérez-Dueñas

  4. Universitat de Barcelona, Barcelona, Spain

    María I. Vanegas

  5. Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau, Barcelona, Spain

    Àlex Bayés

Authors
  1. Ana Cazurro-Gutiérrez
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  2. Anna Marcé-Grau
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  3. Marta Correa-Vela
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  4. Ainara Salazar
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  5. María I. Vanegas
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  6. Alfons Macaya
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  7. Àlex Bayés
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  8. Belén Pérez-Dueñas
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Contributions

All authors contributed to drafting and critically reviewing the manuscript.

Corresponding author

Correspondence to Belén Pérez-Dueñas.

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Supplementary Information

Supplementary Table 1

Updated list of SGCE (NM_003919) variants associated to MD; last revised March 17th, 2021. Clinical significance is established according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Abbreviations: P, pathogenic; LP, likely pathogenic; VUS, variant of uncertain significance; B, benign (DOCX 45.4 kb)

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Cazurro-Gutiérrez, A., Marcé-Grau, A., Correa-Vela, M. et al. ε-Sarcoglycan: Unraveling the Myoclonus-Dystonia Gene. Mol Neurobiol 58, 3938–3952 (2021). https://doi.org/10.1007/s12035-021-02391-0

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  • DOI: https://doi.org/10.1007/s12035-021-02391-0

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