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Mian Li, MD, PhD; Dennis W. Dickson, MD; Alfred J. Spiro, MD

Arch Neurol. 1997;54(12):1457-1461.

Abstract
Background
Laminin 2 is a major component of the basal lamina of skeletal muscle cells. It is a heterotrimer composed of 3 chains: merosin (laminin 2 chain), β₁, and ₁. Deficiency of merosin, with or without laminin β₁ chain reduction, is associated with some forms of congenital muscular dystrophy. Deficient expression of laminin β₁ chain is also associated with some cases of merosin-positive congenital muscular dystrophy. The expression of laminin 2 subunits has not been well studied in the skeletal muscle of limb-girdle muscular dystrophy (LGMD), nor has much attention been given to the significance of reduction of individual laminin 2 subunits, such as β₁.

Objectives
To examine the expression of laminin 2 subunits in skeletal muscle in patients with LGMD and to define the clinical features of patients with LGMD who have abnormal expression of laminin 2 subunits.

Methods
We studied muscle biopsy specimens from 18 patients with LGMD using immunofluorescence with antibodies against dystrophin C-terminus, β-dystroglycan, -sarcoglycan, -sarcoglycan, and the laminin subunits merosin, β₁, and ₁. Of the 18 biopsy specimens, 9 were available for electron microscopic examination of the muscle basement membrane. The clinical features associated with abnormal laminin β₁ chain immunoreactivity were further described.

Results
Laminin β₁ chain was either barely detectable or severely reduced in 3 cases of patients with LGMD in which the biopsy specimens showed normal staining with the other antibodies. Patients in all 3 cases had common clinical features consistent with a slowly progressive, adultonset LGMD. Specimens from 2 of the 3 cases that were available for ultrastructural examination showed significant abnormalities of the muscle fiber basement membrane.

Conclusions
Abnormal expression of laminin β₁ chain without concomitant deficiency of -sarcoglycan in skeletal muscle has not been previously described in LGMD. Reduced laminin β₁ chain immunoreactivity may potentially serve as a marker for defining subsets of individuals with LGMD, in particular those with slowly progressive, adult-onset pelvifemoral presentation. The abnormality of muscle fiber basement membranes in specimens from cases that were available for ultrastructural study suggests that defects in the extracellular matrix may play a role in the pathogenesis of this subset of LGMD.

Author Affiliations
From the Departments of Neurology and Pathology, Albert Einstein College of Medicine, Bronx, NY.

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