Synemin is a member of the intermediate
protein superfamily. Previous studies in avian and rodent skeletal and cardiac muscles have demonstrated that
synemin localises at the Z-band, where it associates with
desmin and
alpha-actinin. In the present study, the distribution of
synemin was examined using immunohistochemistry in muscle biopsy specimens from patients suffering from
myofibrillar myopathy (MM, n=6),
dermatomyositis (DM, n=3),
inclusion body myositis (IBM, n=5),
oculopharyngeal muscular dystrophy (OPD, n=3) and
denervation atrophy (DA, n=3), to investigate the possible participation of this
protein in the pathogenesis of various
muscular diseases. Of patients affected by MM, two showed the presence of mutations in the
desmin gene; none had mutations in the alphaB-
crystallin gene; and no mutations were identified in
synemin or syncoilin genes of three patients.
Synemin immunohistochemistry disclosed a faint staining corresponding to the Z-bands in the cytoplasm of control muscle fibres; in contrast, focal aggregates of
synemin were seen in patients with MM. Increased
synemin immunoreactivity was identified diffusely or in the subsarcolemmal space of scattered fibres in patients with DM, and in vacuolated fibres of patients with IBM and OPD. Strong
synemin immunoreactivity was observed in target formations and atrophic fibres of patients with denervating disorders, as well as in atrophic fibres, regardless of their origin, in all patients studied.
Synemin co-localised with
desmin, as seen on consecutive serial sections immunostained with anti-
synemin or anti-
desmin antibodies. These observations demonstrate abnormal accumulations containing both
synemin and
desmin in muscle fibres in patients with MM, IBM, DM, OPD and DA. Considering the important role of
synemin as one of intermediate filaments of skeletal and cardiac muscle, its destruction and accumulation in the intracellular debris suggest that
synemin may participate in the pathogenesis of these disorders.