Molecular signatures of inherited and acquired sporadic late onset

Acquired sporadic late onset nemaline myopathy (SLONM) and inherited nemaline myopathy (iNM) both feature accumulation of nemaline rods in muscle fibers. Unlike iNM, SLONM is amenable to therapy. The distinction between these disorders is therefore crucial when the diagnosis remains ambiguous after initial investigations. We sought to identify biomarkers facilitating this distinction and to investigate the pathophysiology of nemaline rod formation in these different disorders. Twenty-two muscle samples from patients affected by SLONM or iNM underwent quantitative histological analysis, laser capture microdissection for proteomic analysis of nemaline rod areas and rod-free areas, and transcriptomic analysis. In all iNM samples, nemaline rods were found in subsarcolemmal or central aggregates, whereas they were diffusely distributed within muscle fibers in most SLONM samples. In SLONM, muscle fibers harboring nemaline rods were smaller than those without rods. Necrotic fibers, increased endomysial connective tissue, and atrophic fibers filled with nemaline rods were more common in SLONM. Proteomic analysis detected differentially expressed proteins between nemaline rod areas and rod-free areas, as well as between SLONM and iNM. These differentially expressed proteins implicated immune, structural, metabolic, and cellular processes in disease pathophysiology. Notably, immunoglobulin overexpression with accumulation in nemaline rod areas was detected in SLONM. Transcriptomic analysis corroborated proteomic findings and further revealed substantial gene expression differences between SLONM and iNM. Overall, we identified unique pathological and molecular signatures associated with SLONM and iNM, suggesting distinct underlying pathophysiological mechanisms. These findings represent a step towards enhanced diagnostic tools and towards development of treatments for SLONM.

T-cell dysregulation and inflammatory process in Gcn2 (Eif2ak4

Mitigating age-related somatic mutation burden: Trends in

Modulation of Myosin Regulatory light chains (RLC) and Myosin

Proteomics of brain, CSF, and plasma identifies molecular

Loop Stefan Nicolau

Labroots Genetics Week Virtual Event Series 2022

Artificial Intelligence in Molecular Medicine

Single-Cell Epigenomics and Functional Fine-Mapping of

Human SOX17 Antibody AF1924: R&D Systems

Figure 8 from Regional distribution of synaptic markers and APP

The cytoskeleton in neurodegenerative diseases - Cairns - 2004