LAMININ ABNORMALITY IN SEVERE CHILDHOOD AUTOSOMAL RECESSIVE MUSCULAR-DYSTROPHY

BACKGROUND: In skeletal muscle, dystrophin exists in a large oligomeri c complex tightly associated with several novel sarcolemmal proteins, including the 50-kDa transmembrane glycoprotein called adhalin. The dy strophin-glycoprotein complex links the subsarcolemmal actin cytoskele ton to the basal lamina component laminin, thus providing stability to the sarcolemma. Disturbance of this linkage due to the absence of dys trophin plays a crucial role in the molecular pathogenesis of muscle f iber necrosis in Duchenne muscular dystrophy. Severe childhood autosom al recessive muscular dystrophy (SCARMD) is similar to Duchenne muscul ar dystrophy in phenotype but is characterized by the deficiency of ad halin. At present, the status of the link between the dystrophin-glyco protein complex and laminin is unclear in SCARMD. EXPERIMENTAL DESIGN: We investigated, by immunohistochemistry using confocal laser scannin g microscopy, the status of the expression of laminin subunits, A, M, B1, B2, and S chains, in skeletal muscle biopsy specimens of eight SCA RMD patients from various human populations. In addition, we correlate d the severity of laminin abnormality with the severity of both clinic al symptoms and histopathologic changes in these patients. RESULTS: Th e reduction of laminin B1 chain and the overexpression of the S chain, a homologue of B1, in the extrajunctional basal lamina were observed in the five patients who had advanced clinical symptoms and histopatho logic changes. Abnormalities in the expression of laminin were not obs erved in the three less affected patients. CONCLUSIONS: The expression of laminin is greatly disturbed in severely diseased SCARMD muscle de ficient in adhalin. Disturbance of sarcolemma-basal lamina interaction may play an important role in the molecular pathogenesis of muscle fi ber necrosis in SCARMD.