Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy.

ABSTRACT:

Objectives

We sought to further define the role of sarcomere mutations in dilated cardiomyopathy (DCM) and associated clinical phenotypes.

Background

Mutations in several contractile proteins contribute to DCM, but definitive evidence for the roles of most sarcomere genes remains limited by the lack of robust genetic support.

Methods

Direct sequencing of 6 sarcomere genes was performed on 334 probands with DCM. A novel D230N missense mutation in the gene encoding alpha-tropomyosin (TPM1) was identified. Functional assessment was performed by the use of an in vitro reconstituted sarcomere complex to evaluate ATPase regulation and Ca(2+) affinity as correlates of contractility.

Results

TPM1 D230N segregated with DCM in 2 large unrelated families. This mutation al

SUBMITTER: Lakdawala NK 

PROVIDER: S-EPMC3000630 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature