title: Abnormal expression of laminin beta 1 chain in skeletal muscle of adult-onset limb-girdle muscular dystrophy.
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 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
authors.forename: A J
authors.initials: AJ
authors.lastname: Spiro
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D007797:Laminin; C058783:laminin beta2