Abnormal expression of laminin beta 1 chain in skeletal muscle of adult-onset limb-girdle muscular dystrophy
M. Li, D. W. Dickson and A. J. Spiro
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
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
alpha 2 chain), beta 1, and gamma 1. Deficiency of merosin, 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-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 beta 1. 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, beta-dystroglycan,
alpha-sarcoglycan, gamma-sarcoglycan, and the laminin subunits merosin,
beta 1, and gamma 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 beta 1 chain
immunoreactivity were further described. RESULTS: Laminin beta 1 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, adult-onset 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 beta 1 chain without
concomitant deficiency of alpha-sarcoglycan in skeletal muscle has not been
previously described in LGMD. Reduced laminin beta 1 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.
