Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion

✍ Scribed by Michael W. Lawlor; Elizabeth T. DeChene; Emily Roumm; Amelia S. Geggel; Behzad Moghadaszadeh; Alan H. Beggs

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 369 KB
• Volume: 31
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.21157

✦ Synopsis

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.