Key Points
- To identify specific submicroscopic structural alterations in muscle fibers and elucidate the sequential pathogenic mechanisms driving dysferlinopathy.
- Conducted histological, immunohistochemical, and ultrastructural examinations of muscle biopsy samples from 10 patients with molecularly confirmed dysferlinopathy.
- Histology and immunohistochemistry demonstrated prominent inflammatory responses alongside active muscle regeneration in most patient biopsies.
- Non-necrotic fibers exhibited sarcolemmal gaps, microvilli-like projections, a multilayered basal lamina, and prominent subsarcolemmal aggregations of small vesicles derived from swollen Golgi cisternae.
- Subsarcolemmal vesicle accumulation provided ultrastructural confirmation of an impaired membrane repair system that fails to reseal the sarcolemma.
Structured PICO
PPopulation10 muscle biopsies from patients with molecularly diagnosed dysferlinopathy
OOutcomeSpecific alterations of muscle fibres and sequential mechanism of myopathy developmentsurrogate
Ultrastructural analysis of muscle biopsies from dysferlinopathy patients reveals crowded vesicles beneath the sarcolemma, supporting a defective membrane repair mechanism.