Cap disease due to mutation of the beta-tropomyosin gene (TPM2).
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.
Clarke
Nigel F
NF
Institute for Neuromuscular Research, Children's Hospital at Westmead, Discipline of Paediatrics and Child Health, University of Sydney, Westmead, NSW, Australia.
Domazetovska
Ana
A
Waddell
Leigh
L
Kornberg
Andrew
A
McLean
Catriona
C
North
Kathryn N
KN
D000293:Adolescent; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012518:Sarcomeres / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion / Q000235:genetics*; D014335:Tropomyosin / Q000235:genetics* / Q000378:metabolism
D005819:Genetic Markers; D014335:Tropomyosin; D018698:Glutamic Acid