Molecular Mechanisms

Mutations in LMNA produce up to eight different disorders, now called laminopathies, and it is not clear how they do so. To date, 35 LMNA mutations have been identified in autosomal-dominant FDCM with conduction disease without associated skeletal symptoms: 23 missense and 6 nonsense mutations, and 6 insertions/deletions with frameshift leading to truncated proteins. These mutations are located all along the gene, with 31 being common to both lamins A and C, 1 being specific for lamin C, and 3 being specific for lamin A. More than 101 LMNA mutations have been identified in families with autosomal-dominant skeletal myopathies (EDMD or LGMD1B), in which DCM-conduction defect is a constant feature at an adult age. These mutations are located all along the gene. Thus there is no specific ''DCM-restricted domain'' in lamin A/C.

Mutations in sarcomeric genes can cause both FDCM and familial hypertrophic cardiomyopathy (FHC). Sarcomeric gene mutations in the two distinct clinical entities can result in energetic compromise and alterations in myofibrillar calcium sensitivity, suggesting a unifying pathophysiological mechanism in both FDCM and FHC.

Mutations in cytoskeletal proteins leading to FDCM are thought to produce reduced force transmission from the sarcomere to the extracellular matrix (for review, see Ref. [17]).

Mechanisms by which FDCM is associated with skeletal symptoms still need to be elucidated. A possible key role might be attributed to modifier genes, which influence phenotype expressivity. Environmental factors may contribute to phenotypical variability.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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