Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade

http://distrofiamuscular.net/perindopril_followup.pdf

Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years' follow-up

107th ENMC International Workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, Naarden, the Netherlands

Hereditary muscular dystrophies and the heart

The limb-girdle muscular dystrophies are a diverse group of muscle-wasting disorders characteristically affecting the large muscles of the pelvic and shoulder girdles. Molecular genetic analyses have demonstrated causative mutations in the genes encoding a disparate collection of proteins involved in all aspects of muscle cell biology. Muscular dystrophy includes a spectrum of disorders caused by loss of the linkage between the extracellular matrix and the actin cytoskeleton. Within this are the forms of limb-girdle muscular dystrophy caused by deficiencies of the sarcoglycan complex and by aberrant glycosylation of alpha-dystroglycan caused by mutations in the fukutin-related protein gene. However, other forms of this disease have distinct pathophysiological mechanisms. For example, deficiency of dysferlin disrupts sarcolemmal membrane repair, whilst loss of calpain-3 may exert its pathological influence either by perturbation of the IkappaBalpha/NF-kappaB pathway, or through calpain-dependent cytoskeletal remodelling. Caveolin-3 is implicated in numerous cell-signalling pathways and involved in the biogenesis of the T-tubule system. Alterations in the nuclear lamina caused by mutations in laminA/C, sarcomeric changes in titin, telethonin or myotilin at the Z-disc, and subtle changes in the extracellular matrix proteins laminin-alpha2 or collagen VI can all lead to a limb-girdle muscular dystrophy phenotype, although the specific pathological mechanisms remain obscure. Differential diagnosis of these disorders requires the careful application of a broad range of disciplines: clinical assessment, immunohistochemistry and immunoblotting using a panel of antibodies and extensive molecular genetic analyses.

Limb‐girdle muscular dystrophies – from genetics to molecular pathology

http://vincenzonigro.it/politano nd 01.pdf

P.F Rambaldi

Papers

Evaluation of cardiac and respiratory involvement in sarcoglycanopathies.