Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. Hum Mutat 2010 Feb;31(2):176-83
Date
12/03/2009Pubmed ID
19953533Pubmed Central ID
PMC2815199DOI
10.1002/humu.21157Scopus ID
2-s2.0-75149179143 (requires institutional sign-in at Scopus site) 71 CitationsAbstract
Congenital fiber type disproportion (CFTD) is a rare congenital myopathy characterized by hypotonia and generalized muscle weakness. Pathologic diagnosis of CFTD is based on the presence of type 1 fiber hypotrophy of at least 12% in the absence of other notable pathological findings. Mutations of the ACTA1 and SEPN1 genes have been identified in a small percentage of CFTD cases. The muscle tropomyosin 3 gene, TPM3, is mutated in rare cases of nemaline myopathy that typically exhibit type 1 fiber hypotrophy with nemaline rods, and recently mutations in the TPM3 gene were also found to cause CFTD. We screened the TPM3 gene in patients with a clinical diagnosis of CFTD, nemaline myopathy, and with undefined congenital myopathies. Mutations in TPM3 were identified in 6 out of 13 patients with CFTD, as well as in one case of nemaline myopathy. Review of muscle biopsies from patients with diagnoses of CFTD revealed that patients with a TPM3 mutation all displayed marked disproportion of fiber size, without type 1 fiber predominance. Several mutation-negative cases exhibited other abnormalities, such as central nuclei and central cores. These results support the utility of the CFTD diagnosis in directing the course of genetic testing.
Author List
Lawlor MW, Dechene ET, Roumm E, Geggel AS, Moghadaszadeh B, Beggs AHAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultChild
Female
Genetic Predisposition to Disease
Humans
Infant
Infant, Newborn
Male
Middle Aged
Muscle Fibers, Skeletal
Mutation
Myopathies, Nemaline
Myopathies, Structural, Congenital
Tropomyosin
