Expression of cytoskeleton proteins in central core disease

Abstract Despite advances in genetics the pathogenesis of central core disease (CCD) is still unknown. We studied muscles from 5 CCD patients by immunocytochemistry using monoclonal antibodies against various cytoskeletal proteins (dystrophin, spectrin, vinculin, desmin, vimentin, myosin heavy chain (MHC) of developmental, neonatal, adult slow and fast types). Dystrophin, spectrin and vinculin immunoreactivity was localized only at sarcolemma as in normal muscle. Vimentin was not present in myofibers. Only sporadic fibers were positive for developmental and neonatal MHC isoforms in adult CCD muscles. A 4-month-old patient had 5% of neonatal MHC-immunoreactive fibers, a finding similar to that of age-matched normal muscle. Desmin intermediate filaments were overexpressed in many core-fibers in extra-core regions, reduced or absent at cores, and greatly increased at the periphery of some cores. Moreover, irregular desmin-positive spots were seen within some cores. On the contrary, in neurogenic muscle atrophy patients, target lesions had increased desmin. These features indicate a possible role of desmin in the pathogenesis of cores, although we do not know if primary or secondary. In addition, they suggest that: (i) cores and targets may be manifestations of different processes; (ii) it is likely that core-fibers are not denervated fibers.