Immunophenotyping of congenital myopathies: disorganization of sarcomeric, cytoskeletal and extracellular matrix proteins

W e have studied the expression and distribution patterns of the interm ediate filam ent proteins desm in and vimentin, the sarcomere com ponents titin, nebulin and myosin, the basem ent membrane constituents collagen type IV and laminin, and the reticular layer com ponent collagen type VI in skeletal m uscle of patients w ith “classic” congenita l m yopathies (CM), using indirect im m unofluorescence assays. In all biopsy specimens obtained from patients with central core disease (C C D ), nem aline myopathy (N M ), X -linked myotubular myopathy (XLM TM ) and centronuclear m yopathy (C N M ), d isease-specific desm in disturbances w ere observed. Vim entin was present in immature fibres in severe neonatal N M , and as sarcoplasm ic aggregates in one case of CNM , w hile the amounts of vimentin and embryonic myosin, observed in X L M T M , decreased w ith age o f the patients. Abnorm al expression of myosin isoforms was found in several CM biopsies, although the organization o f myosin and other sarcomere com ponents was rarely disturbed. Basem ent membrane and reticular layer proteins were o ften prominently increased in severe cases o f CM. W e conclude that (i) desmin is a marker for individual types o f CM and m ight be used for diagnostic purposes; (ii) the expression patterns of the differentiation markers desm in, v im entin and embryonic myosin in XLM TM , point either to a postnatal muscle fibre maturation or to a variable tim e-point o f m aturational arrest in individual patients; (iii) the correlation between the distribution patterns of extracellular matrix proteins and clinical presentation points to a role of these proteins in pathophysiology of CM.