Abstract
Cap disease or cap myopathy is a form of congenital myopathy in which peripheral, well-demarcated 'caps' of disorganised thin filaments are seen in muscle fibres. Mutation of the TPM2 gene, that encodes beta-tropomyosin, is the first reported genetic cause. In this paper, we describe a further case of cap disease due to a mutation in TPM2, confirming the importance of this genetic association. This is the first report of cardiac dysfunction due to a mutation in TPM2. Our patient has an identical TPM2 mutation to the first genetically diagnosed cap disease patient, a denovo heterozygous three base pair deletion that removes glutamic acid 139 from the centre of beta-tropomyosin (p.E139del). 2D-gel electrophoresis studies show that the shortened mutant protein incorporates into sarcomeric structures, where it likely imposes a dominant-negative effect to cause muscle weakness.
Publication types
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Amino Acid Sequence / genetics
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Base Sequence / genetics
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Cardiomyopathies / genetics*
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Cardiomyopathies / metabolism
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Cardiomyopathies / physiopathology
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DNA Mutational Analysis
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Female
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Genetic Markers / genetics
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Genetic Predisposition to Disease / genetics*
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Genotype
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Glutamic Acid / metabolism
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Humans
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Muscle Fibers, Skeletal / metabolism*
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Muscle Fibers, Skeletal / pathology
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Muscle Weakness / genetics
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Muscle Weakness / metabolism
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Muscle Weakness / pathology
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiopathology
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Muscular Diseases / genetics*
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Muscular Diseases / metabolism
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Muscular Diseases / pathology
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Myocardium / metabolism
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Myocardium / pathology
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Sarcomeres / genetics
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Sarcomeres / metabolism
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Sarcomeres / pathology
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Sequence Deletion / genetics*
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Tropomyosin / genetics*
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Tropomyosin / metabolism
Substances
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Genetic Markers
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Tropomyosin
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Glutamic Acid