Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) results in part from genetic disorders. Recently, missense mutations of the cardiac actin gene have been reported to cause DCM. We studied 136 Japanese DCM cases to elucidate how frequently the gene mutations are involved in its pathogenesis. Genomic DNA samples were obtained from 136 DCM cases (107 males, 29 females), containing 30 familial DCM (5 confirmed and 25 suspected). All six exons of the cardiac actin gene were analyzed by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. We detected no mutations of the disease causation previously reported (G867A or A1014G) but two silent mutations (G979C and C1018T) in exon 6 and one point mutation (T1080A) in the 3'-untranslated region. As a result of screening 128 healthy subjects, these novel silent mutations were found to be mere genetic polymorphisms, not responsible for the disease. Although some genetic polymorphisms exist in the cardiac actin gene, mutations of the gene are rarely responsible for DCM, at least in the Japanese patients.

Molecular genetics of familial hypertrophic cardiomyopathy (FHC)

“…The gene has a p.A295S mutation in exon 5, which results in impaired myosin binding by the protein, leading to impaired force generation and, hence, compensatory hypertrophy. Mutations in this gene can also cause inherited idiopathic dilated cardiomyopathy (IDC) (Takai et al 1999). Mogensen and coworkers (1999) have shown in their study that mutations affecting sarcomere contraction led to FHC, whereas mutations affecting force transmission from the sarcomere to the surrounding syncytium led to IDC.…”

Suppressive Effect of the Gly389 Allele of the .BETA.1-Adrenergic Receptor Gene on the Occurrence of Ventricular Tachycardia in Dilated Cardiomyopathy.

“…11,12 All DCM patients underwent invasive and noninvasive evaluation, including a physical examination, ECG, chest X ray, M-mode and 2-dimensional echocardiography, diagnostic right and left cardiac catheterization with coronary angiography and left ventriculography, as reported previously. 13 Patients with at least 50% stenosis of the major coronary arteries, myocardial infarction, documented myocarditis, and specific primary or secondary heart muscle diseases, were excluded. Complete 24 h-Holter ECG recordings were available in 133 of 163 patients (81.6%).…”

Genetics and dilated cardiomyopathy: limitations of candidate gene strategies

“…The addition of 86 cases from the current study by Tesson et al [7] brings to over 270 the total number screened and adds a European cohort to the Japanese and African populations already studied. No mutations have been identified in any of these individuals suggesting that -cardiac actin mutations rarely, if ever, cause dilated cardiomyopathy [7,12,13] . To add to the uncertainty, mutations in the same domain of -cardiac actin have also been described in a single family with hypertrophic cardiomyopathy where there is ventricular dilatation late in the course of disease [14] .…”

“…While these substitutions did occur in conserved residues and were not seen in a large control population, again there was no evidence of linkage and there are no functional data. Several groups have attempted to replicate these findings in dilated cardiomyopathy probands from a variety of populations [12,13] . The addition of 86 cases from the current study by Tesson et al [7] brings to over 270 the total number screened and adds a European cohort to the Japanese and African populations already studied.…”