VMA21 deficiency leads to autophagic dysregulation and altered vesicle trafficking in X-linked myopathy with excessive autophagy - Report - MDSpire

VMA21 deficiency leads to autophagic dysregulation and altered vesicle trafficking in X-linked myopathy with excessive autophagy

  • By

  • Christian A. Suarez

  • Sara K. Pittman

  • Michio Inoue

  • Eileen M. Lynch

  • Andrew Moran

  • Angèle N. Merlet

  • Emmanuelle Lacenne

  • Teresinha Evangelista

  • Conrad C. Weihl

  • June 26, 2026

  • 0 min

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Deficiency of VMA21 Results in Autophagy Disruption in X-Linked Myopathy

Overview

This study investigates the role of VMA21 deficiency in X-linked myopathy characterized by excessive autophagy. The findings demonstrate that loss of VMA21 leads to disrupted autophagy and vesicular transport.

Background

X-linked myopathy with excessive autophagy (XMEA) is a rare neuromuscular disorder primarily affecting males, characterized by progressive muscle weakness and autophagic vacuoles in muscle tissue.

Data Highlights

No numerical data or trial data provided in the source material.

Key Findings

  • VMA21 mutations disrupt V-ATPase assembly, leading to lysosomal dysfunction.
  • XMEA is characterized by the presence of autophagic vacuoles with sarcolemmal features.
  • Histopathological analysis reveals cytoplasmic vacuoles and complex fiber splitting in muscle tissue.
  • Skeletal muscle-specific Vma21 deletion in mice recapitulates the pathological features of XMEA.
  • Combined skeletal and cardiac muscle deletion results in early lethal cardiomyopathy with autophagic impairment.

Clinical Implications

The study highlights the importance of VMA21 in lysosomal function and autophagy regulation in XMEA.

Conclusion

The findings provide insights into the pathogenesis of XMEA.

Related Resources & Content

  1. Recent advances in the clinical spectrum and pathomechanisms associated with X-linked myopathy with excessive autophagy and other VMA21-related disorders, 2023 -- Title
  2. X-linked myopathy with excessive autophagy - NIH Genetic Testing Registry (GTR), NCBI -- Title
  3. Brain — Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot–Marie–Tooth type 1B
  4. Acta Neuropathologica — Induction of Autophagy Prevents Axonal Degeneration in a Mouse Model of X-Adrenoleukodystrophy
  5. Acta Neuropathologica — Comprehensive Multiomic Analysis of a 99-mer Repeat Expansion in a Hereditary Skeletal Muscle Disorder
  6. Brain — Interplay Between Lymphotoxin-Induced Myositis and Autophagy Dysfunction in Mouse Muscle Models
  7. Recent advances in the clinical spectrum and pathomechanisms associated with X-linked myopathy with excessive autophagy and other VMA21-related disorders
  8. X-linked myopathy with excessive autophagy - NIH Genetic Testing Registry (GTR) - NCBI
  9. EAN 2024 Guideline on the Diagnostic Approach to Oligo/Asymptomatic HyperCKemia - PMC
  10. X-linked myopathy with excessive autophagy: characterization and therapy testing in a zebrafish model - PMC
  11. X-linked myopathy with excessive autophagy: characterization and therapy testing in a zebrafish model | EMBO Molecular Medicine | Springer Nature Link

Original Source(s)

VMA21 deficiency leads to autophagic dysregulation and altered vesicle trafficking in X-linked myopathy with excessive autophagy

  • by Christian A. Suarez, Sara K. Pittman, Michio Inoue, Eileen M. Lynch, Andrew Moran, Angèle N. Merlet, Emmanuelle Lacenne, Teresinha Evangelista, Conrad C. Weihl

  • June 26, 2026

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