Abnormal expression of laminin beta 1 chain in skeletal muscle of adult-onset limb-girdle muscular dystrophy
| Autor: | Mian Li, Alfred J. Spiro, Dennis W. Dickson |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
musculoskeletal diseases
Adult Male Pathology medicine.medical_specialty Adolescent Muscular Dystrophies Arts and Humanities (miscellaneous) Laminin medicine Humans Muscular dystrophy Age of Onset Child Muscle Skeletal Aged Muscle biopsy medicine.diagnostic_test biology Skeletal muscle Middle Aged medicine.disease Immunohistochemistry Microscopy Electron medicine.anatomical_structure Congenital muscular dystrophy biology.protein Female Neurology (clinical) Dystrophin ITGA7 Limb-girdle muscular dystrophy |
| Zdroj: | Archives of neurology. 54(12) |
| ISSN: | 0003-9942 |
| Popis: | 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 α2 chain), β 1 , and γ 1 . Deficiency of merosin, with or without laminin β 1 chain reduction, is associated with some forms of congenital muscular dystrophy. Deficient expression of laminin β 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 β 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, β-dystroglycan, α-sarcoglycan, γ-sarcoglycan, and the laminin subunits merosin, β 1 , and γ 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 β 1 chain immunoreactivity were further described. Results: Laminin β 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, 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 β 1 chain without concomitant deficiency of α-sarcoglycan in skeletal muscle has not been previously described in LGMD. Reduced laminin β 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. |
| Databáze: | OpenAIRE |
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