ABNORMAL EXPRESSION OF LAMININ BETA(1) CHAIN IN SKELETAL-MUSCLE OF ADULT-ONSET LIMB-GIRDLE MUSCULAR-DYSTROPHY

Background: Laminin 2 is a major component of the basal lamina of skel etal muscle cells. It is a heterotri mer composed of 3 chains: merosin (laminin alpha(2), chain), beta(1) and gamma(1). Deficiency of merosi n, with or without laminin beta(1) chain reduction, is associated with some forms of congenital muscular dystrophy. Deficient expression of laminin beta(1) chain is also associated with some cases of merosin-po sitive congenital muscular dystrophy. The expression of laminin 2 subu nits has not been well studied in the skeletal muscle of limb-girdle m uscular dystrophy (LGMD), nor has much attention been given to the sig nificance of reduction of individual laminin 2 subunits, such as beta( 1). Objectives: To examine the expression of laminin 2 subunits in ske letal muscle in patients with LGMD and to define the clinical features -of patients with LGMD who have abnormal expression of laminin 2 subun its. Methods: We studied muscle biopsy specimens from 18 patients with LGMD using immunofluorescence with antibodies against dystrophin C-te rminus, beta-dystroglycan, alpha-sarcoglycan, gamma-sarcoglycan, and t he laminin subunits merosin, beta(1), and gamma(1). Of the 18 biopsy s pecimens, 9 were available for electron microscopic examination of the muscle basement membrane. The clinical features associated with abnor mal laminin beta(1) chain immunoreactivity were further described. Res ults: laminin beta(1) chain was either barely detectable or severely r educed in 3 cases of patients with LGMD in which the biopsy specimens showed normal staining with the other antibodies. Patients in all 3 ca ses had common clinical features consistent with a slowly progressive, adult-onset LGMD. Specimens from 2 of the 3 cases that were available for ultrastructural examination showed significant abnormalities of t he muscle fiber basement membrane. Conclusions: Abnormal expression of laminin beta(1) chain without concomitant deficiency of alpha-sarcogl ycan in skeletal muscle has not been previously described in LGMD. Red uced laminin beta(1) chain immunoreactivity may potentially serve as a marker for defining subsets of individuals with LGMD, in particular t hose with slowly progressive, adult-onset pelvifemoral presentation. T he abnormality of muscle fiber basement membranes in specimens from ca ses that were available for ultrastructural study suggests that defect s in the extracellular matrix may play a role in the pathogenesis of t his subset of LGMD.