TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.

ABSTRACT:

Objective

Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient.

Methods

The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224.

Results

Contractility studies on permeabilized myofibers demonstrated reduced maximal active tens

SUBMITTER: Donkervoort S 

PROVIDER: S-EPMC5154623 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature