Brain of miyoshi myopathy/dysferlinopathy patients presents with structural and metabolic anomalies
Miyoshi myopathy/dysferlinopathy (MMD) is a rare muscle disease caused by DYSF gene mutations. Apart from skeletal muscles, DYSF is also expressed in the brain. However, the impact of MMD-causing DYSF variants on brain structure and function remains unexplored. To investigate this, we utilized magnetic resonance (MR) modalities (MR volumetry and <sup>31</sup>P MR spectroscopy) in a family with seven children, four of whom have the illness. The MMD siblings showed distinct differences from healthy controls: (1) a significant (p < 0.001) right-sided volume asymmetry (+ 232 mm<sup>3</sup>) of the inferior lateral ventricles; and (2) a significant (p < 0.001) decrease in [Mg<sup>2+</sup>], along with a modified energy metabolism profile and altered membrane turnover in the hippocampus and motor and premotor cortices. The patients' [Mg<sup>2+</sup>], energy metabolism, and membrane turnover measures returned to those of healthy relatives after a month of 400 mg/day magnesium supplementation. This work is the first to describe anatomical and functional abnormalities characteristic of neurodegeneration in the MMD brain. Therefore, we call for further examination of brain functions in larger cohorts of MMD patients and testing of magnesium supplementation, which has proven to be an effective corrective approach in our study.
Authors
- Martin Kolísek (ORCID: https://orcid.org/0000-0001-8962-4511)
- Martin Krššák (ORCID: https://orcid.org/0000-0001-9717-803X)
- J. K. Grossmann (ORCID: https://orcid.org/0000-0002-2957-3553)
- Wolfgang Bogner (ORCID: https://orcid.org/0000-0002-0130-3463)
- Ivica Just
- Egon Kurča (ORCID: https://orcid.org/0000-0002-1025-6830)
- Petra Hnilicová (ORCID: https://orcid.org/0000-0003-1529-1675)
- Peter Špalek
- Jana Harsányiová (ORCID: https://orcid.org/0000-0002-8195-3844)
- Iveta Mečiarová
- N Misovicová
- Norbert Žilka (ORCID: https://orcid.org/0000-0003-2397-2083)
- Marian Grendár (ORCID: https://orcid.org/0000-0002-6712-3457)
- Martina Hikkelová
- Kamil Zeleňák (ORCID: https://orcid.org/0000-0002-0416-2985)
- Monika Turčanová Koprušáková (ORCID: https://orcid.org/0000-0002-7864-6560)
- A. Králová
Institutions
- Slovak Medical University (SK)
- Slovak Academy of Sciences (SK)
- University Hospital Bratislava (SK)
- Institute of Plant Genetics and Biotechnology of the Slovak Academy of Sciences (SK)
- Institute of Neuroimmunology of the Slovak Academy of Sciences (SK)
- Martin University Hospital (SK)
- Comenius University Bratislava (SK)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-08-20
- DOI
- https://doi.org/10.1038/s41598-024-69966-4
- Citations
- 2
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Univerzita Komenského v Bratislave
- Bundesministerium für Wissenschaft, Forschung und Wirtschaft
- Agentúra na Podporu Výskumu a Vývoja
- Bundesministerium für Bildung, Wissenschaft und Forschung