Clinical and histopathological features of abnormalities of the dystrophin-based membrane cytoskeleton.
The majority (approximately 70%) of cases of childhood and adult onset muscular dystrophies in males, and approximately 10% of dystrophy in girls and women, show underlying primary abnormalities of dystrophin. Approximately 2% of childhood/adult onset muscular dystrophy patients have a primary defect of one of the three sarcoglycan proteins identified to date (alpha, beta, gamma). The finding of a sarcoglycan deficiency in muscle generally does not reflect the primary underlying defect, and thus testing of biopsies for sarcoglycans should be used only after normal dystrophin findings, and in conjunction with gene mutation testing. Approximately 30% of neonatal onset congenital muscular dystrophy has been shown to be due alpha 2-laminin (merosin) deficiency. alpha 2-laminin is a component of the myofiber basal lamina, and this protein interacts with the dystrophin-based membrane cytoskeleton. Due to the similar clinical and histopathological features of the different etiologies of muscular dystrophies, molecular testing of peripheral blood DNA and muscle biopsy protein are a critical part of the clinical work-up of dystrophy patients. Many patients carrying a Becker dystrophy or limb-girdle dystrophy diagnosis should be re-evaluated with molecular tests to provide accurate genetic counseling to their families.
Hoffman
E P
EP
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA.
D003599:Cytoskeleton / Q000648:ultrastructure*; D016189:Dystrophin / Q000502:physiology*; D005821:Genetic Techniques; D006801:Humans; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*
D016189:Dystrophin