Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2.
"Cap myopathy" or "cap disease" is a congenital myopathy characterised by cap-like structures at the periphery of muscle fibres, consisting of disarranged thin filaments with enlarged Z discs. Here we report a deletion in the beta-tropomyosin (TPM2) gene causing cap disease in a 36-year-old male patient with congenital muscle weakness, myopathic facies and respiratory insufficiency. The mutation identified in this patient is an in-frame deletion (c.415_417delGAG) of one codon in exon 4 of TPM2 removing a single glutamate residue (p.Glu139del) from the beta-tropomyosin protein. This is expected to disrupt the seven-amino acid repeat essential for making a coiled coil, and thus to impair tropomyosin-actin interaction. Missense mutations in TPM2 have previously been found to cause rare cases of nemaline myopathy and distal arthrogryposis. This mutation is one not previously described and the first genetic cause identified for cap disease.
Lehtokari
Vilma-Lotta
VL
The Folkhälsan Institute of Genetics and the Department of Medical Genetics, University of Helsinki, Helsinki, Finland, and Division of Neurology, University Hospital of Antwerp, Antwerpen, Belgium.
Ceuterick-de Groote
Chantal
C
de Jonghe
Peter
P
Marttila
Minttu
M
Laing
Nigel G
NG
Pelin
Katarina
K
Wallgren-Pettersson
Carina
C
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D019066:Facies; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018908:Muscle Weakness / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012131:Respiratory Insufficiency / Q000473:pathology; D014335:Tropomyosin / Q000235:genetics* / Q000378:metabolism
D000199:Actins; C518659:TPM2 protein, human; D014335:Tropomyosin