Muscle Weakness: New Mutation Identified

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Muscle Weakness: New Mutation Identified

http://www.medicalnewstoday.com/medicalnews.php?newsid=74334

New research, published in The Journal of Physiology, has identified

a novel mutation associated with muscle weakness and distal limb

deformities. The study demonstrates that muscle weakness experienced

by persons with a regulatory protein tropomyosin mutation is

directly related to a mechanism by which the mutant tropomyosin

modulates contractile speed and force-generation capacity.

Dr. n Ochala and co-workers at the Department of Clinical

Neurophysiology, University of Uppsala, in collaboration with

scientists at the Department of Pathology, University of Göteborg,

explored the mechanisms underlying the muscle weakness experienced

by a woman and her daughter with a & #946;-tropomyosin mutation, i.e.,

muscle weakness in the absence of macro or microscopic signs of

muscle wasting. The results from single fibre contractile

measurements and in vitro motility analyses demonstrated a mechanism

where tropomyosin modulates myosin-actin kinetics. A slower motor

protein myosin attachment rate to and a faster detachment rate from

actin, caused by the mutation, results in a reduced number of myosin

molecules in the strong actin binding state and muscle weakness. The

results also implicate a potential role of the regulatory protein

tropomyosin in modulating contractile speed and force-generation

under physiological conditions.

It is suggested that the findings at the gene, protein and muscle

cell levels in this specific neuromuscular disorder will have a

significant impact on our understanding of the disease pathogenesis

and provide important information for future therapeutic strategies.

Walter R. Frontera, an independent expert, says: " Dr. Ochala and

collaborators have published elegant proof of the clinical

consequences of mutations in the regulatory proteins of skeletal

muscles. Their data provide strong support for the dissociation

between qualitative alterations in muscle contractility and

quantitative evidence of muscle atrophy " .