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.

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.

• Authors: M Li, D W Dickson, A J Spiro
• Journal: Archives of neurology (Arch Neurol) Vol. 54 Issue 12 Pg. 1457-61 (Dec 1997) ISSN: 0003-9942 [Print] United States
• PMID: 9400354 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Laminin
• laminin beta2

Topics

• Adolescent
• Adult
• Age of Onset
• Aged
• Child
• Female
• Humans
• Immunohistochemistry
• Laminin (metabolism)
• Male
• Microscopy, Electron
• Middle Aged
• Muscle, Skeletal (metabolism, pathology, physiopathology)
• Muscular Dystrophies (metabolism, pathology, physiopathology)