EXPRESSION OF CYTOSKELETON PROTEINS IN CENTRAL CORE DISEASE

Despite advances in genetics the pathogenesis of central core disease (CCD) is still unknown. We studied muscles from 5 CCD patients by immu nocytochemistry using monoclonal antibodies against various cytoskelet al proteins (dystrophin, spectrin, vinculin, desmin, vimentin, myosin heavy chain (MHC) of developmental, neonatal, adult slow and fast type s). Dystrophin, spectrin and vinculin immunoreactivity was localized o nly at sarcolemma as in normal muscle. Vimentin was not present in myo fibers. Only sporadic fibers were positive for developmental and neona tal 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 overexpresse d in many core-fibers in extra-core regions, reduced or absent at core s, and greatly increased at the periphery of some cores. Moreover, irr egular desmin-positive spots were Seen within some cores. On the contr ary, in neurogenic muscle atrophy patients, target lesions had increas ed desmin. These features indicate a possible role of desmin in the pa thogenesis of cores, although we do not know if primary or secondary. In addition, they suggest that: (i) cores and targets may be manifesta tions of different processes; (ii) it is likely that core-fibers are n ot denervated fibers.