Fig. 8
Previously known and novel pathological abnormalities in XLMTM. Muscles in animal models and patients with XLMTM display smaller muscle fibres and centrally positioned myonuclei. In addition, they display: (1) altered myonuclear organization and synthetic activity; (2) Reduced myofilament density and contractile protein content; (3) abnormal T-tubule and sarcoplasmic reticulum (SR) structure, correlated with impaired Ca2+ release and excitation–contraction coupling; and (4) neuromuscular junction (NMJ) and neurotransmission alterations. Other abnormalities include: altered signaling pathways; protein aggregates (e.g. desmin) potentially caused by blockade of late-stage autophagy and effects on proteasomal degradation pathways; and altered phosphoinositide metabolism (reviewed by [39])