Actin mutations in dilated cardiomyopathy, a heritable form of heart failure.

  title={Actin mutations in dilated cardiomyopathy, a heritable form of heart failure.},
  author={Timothy M. Olson and Virginia V. Michels and Stephen N. Thibodeau and Yun-Shen Tai and Mark T. Brookline Keating},
  volume={280 5364},
To test the hypothesis that actin dysfunction leads to heart failure, patients with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for mutations in the cardiac actin gene (ACTC). Missense mutations in ACTC that cosegregate with IDC were identified in two unrelated families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Coupled with previous data showing that dystrophin mutations also cause dilated… 

The molecular biology of dilated cardiomyopathy


Mutations in sarcomere protein genes account for approximately 10 percent of cases of familial dilated cardiomyopathy and are particularly prevalent in families with early-onset ventricular dilatation and dysfunction, which implicates defects in contractile-force transmission as one mechanism underlying this disorder.

Mutations in the Human δ-Sarcoglycan Gene in Familial and Sporadic Dilated Cardiomyopathy, a Disease of the Cytoskeleton and Sarcolemma

A large number of cases are familial (FDCM), with the remainder appearing sporadically, and autosomal dominant inheritance is the most common form of FDCM, although X-linked disease is also well described.

What makes the heart fail? New insights from defective genes

Recognition of dilated and hypertrophic cardiomyopathies as allelic disorders has provided the opportunity to identify genotype‐phenotype relationships and to gain new insight into pathways leading to cardiac failure and hypertrophy.

α-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy

The alpha-cardiac actin gene (ACTC) is identified as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC), and linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene.

Titin mutations as the molecular basis for dilated cardiomyopathy.

Observations suggest that titin mutations may cause DCM in a subset of the patients, and one of them was a nonsense mutation presumably encoding for a truncated nonfunctional molecule.

Novel Cardiac Troponin T Mutation as a Cause of Familial Dilated Cardiomyopathy

A novel missense mutation in the cardiac troponin T gene is identified by direct sequencing and confirmed by endonuclease restriction analysis in a large family with FDCM and appears that the phenotype, whether it be hypertrophy or dilatation, is determined by the specific mutation rather than the gene.

Classifying Cardiac Actin Mutations Associated With Hypertrophic Cardiomyopathy

This work suggests the classification of ACTC1 mutations based on the location of the resulting amino acid change in actin into three main groups: those affecting only the binding site of the myosin molecular motor, termed M-class mutations, and those affecting both theMyosin- and Tm-binding sites, called MT- class mutations.

Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics

With mounting evidence that thin filament cardiomyopathies occur through a distinct mechanism, there is need for therapies targeting the unique, underlying mechanisms tailored for each patient depending on a given mutation.

Hypertrophy: Clinical Relevance of Genotype

The two major genes are those encoding β-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3) and the clinical relevance of these observations will be discussed.



Familial dilated cardiomyopathy.

A diversity of genetic etiologies in DCM explains why patients sometimes exhibit additional clinical manifestations, including defects in the conduction system resulting in arrhythmias, skeletal muscle abnormalities, deafness, and endocrinologic disease.

Evidence for a dystrophin missense mutation as a cause of X-linked dilated cardiomyopathy.

A novel missense mutation in exon 9 of dystrophin causing an abnormality at H1 leads to the cardiospecific phenotype of XLCM.

Mapping a cardiomyopathy locus to chromosome 3p22-p25.

Haplotype analyses indicate that a gene causing DCM associated with rhythm and conduction abnormalities is located on chromosome 3p, and represent the first step toward disease gene identification.

Management of hypertrophic cardiomyopathy.

Technological developments in implantable defibrillators and pacemakers have provided new therapeutic options for patients with hypertrophic cardiomyopathy and deepened understanding of the disorder and have suggested new approaches to the assessment of prognosis.

The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy.

Dilated cardiomyopathy was found to be familial in at least one in five of the patients in this study, a considerably higher percentage than in previous reports.

Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23.

It is concluded that a new locus for pure autosomal dominant FDCM exists, and that this gene is localized to a 9 cM region of 10q21-10q23, and the search for the disease causing gene and the responsible mutation is ongoing.

Rescue of cardiac α-actin-deficient mice by enteric smooth muscle γ-actin

It is demonstrated that alterations in actin composition in the fetal and adult heart are associated with severe structural and functional perturbations.

Molecular structure and evolutionary origin of human cardiac muscle actin gene.

Two recombinant phages that contain cardiac muscle actin gene were isolated from a human DNA library and their structures were determined, indicating that they are derived from their ancestor gene at a relatively recent time in evolutionary development.