Congenital Myopathies – Nemaline Myopathies

Abstract

Neuromuscular Disorders 31 (2021) S47-S162 Acta1 (H40Y) knock-in mouse model of the disease. We found the presence of fragmented neuromuscular junctions in various muscles, ultrastructural changes in the post-synaptic region, and increased fatigability of the diaphragm upon repeated electrophysiological nerve stimulation in mutant mice. In addition, molecular changes were present in gastrocnemius muscle of Acta1 (H40Y) mice at 1 month of age, when signs of the pathology are present, with deregulated expression of various acetylcholine receptor subunits. Importantly, ultrastructural abnormalities in NMJs were observed in muscle biopsies from patients with ACTA1 mutations. These results strongly suggest that defects in neuromuscular junctions contribute to the pathophysiology of ACTA1 -related nemaline myopathy, and provides the rationale for therapies targeting these structures in patients.