Dystrophin gene abnormalities in two patients with idiopathic dilated cardiomyopathy

Abstract

Two new cases of dilated cardiomyopathy (DC) caused by dystrophinopathy are reported. One patient, a 24 year old man, had a family history of X linked DC, while the other, a 52 year old man, had sporadic disease. Each had abnormal dystrophin immunostaining in muscle or cardiac biopsy specimens, but neither had muscle weakness. Serum creatine kinase activity was raised only in the patient with familial disease. Analysis of dystrophin gene mutations showed a deletion of exons 48-49 in the patient with familial DC and of exons 49-51 in the other. Dystrophin transcription in cardiac tissue from the patient with sporadic disease showed abundant expression, predominantly of the muscle isoform. This study, together with previous reports, suggests that some patients with DC have a dystrophinopathy that can be diagnosed using a combination of biochemical and genetic analyses.

Gene Mutations in Adult Japanese Patients With Dilated Cardiomyopathy

“…Mutations identified in the present study would be categorized as Group B, and all of the present patients had a deletion of exon 48. Muntoni et al 33 and Melacini et al 34 reported that exon 49 was important for cardiac function, and it has also been proposed that intron 48 may contain sequences important to cardiac muscle function. 33 From these findings, we hypothesize that the regions including exons 48 and 49 and intron 48 may be necessary for maintaining cardiac function.…”

“…Muntoni et al 33 and Melacini et al 34 reported that exon 49 was important for cardiac function, and it has also been proposed that intron 48 may contain sequences important to cardiac muscle function. 33 From these findings, we hypothesize that the regions including exons 48 and 49 and intron 48 may be necessary for maintaining cardiac function. In addition, less severe mutations of dystrophin, such as missense mutations, may be associated with the sporadic form of DCM.…”

Antisense Oligonucleotide-Mediated Exon Skipping for Duchenne Muscular Dystrophy: Progress and Challenges

“…DMD and BMD mutations differentially affect the DMD gene: in DMD the mutations disrupt the reading frame, while mutations that cause BMD maintain the ORF (31,32) leading to the production of an internally deleted dystrophin protein. The size of the deletion does not correlate with the severity of the disease, as long as the reading frame rule is maintained (33)(34)(35)(36)(37)(38)(39)(40), and provided crucial domains of dystrophin such as the β-dystroglycan binding site are not removed by the deletion. While the central and distal rod domain is less vital for function (35), (some patients missing these domains only have very mild disease manifestations such as myalgia and muscle cramps, and mild weakness), in frame deletions that affect the binding of dystrophin to other proteins such as cytoskeletal actin or β-dystroglycan result in a severe phenotype (41,42).…”

Cellular and biomolecular mechanisms in dilated cardiomyopathy

“…Inheritance is linked to the X chromosome and can be dominant or recessive 51 . Sporadic cases are reported 50 . Prevalence of disorders involving dystrophin in DCM patients is still unknown.…”

“…Anomalies affecting the gene codifying this substance cause Duchenne's dystrophy and Becker type muscular dystrophy. In rare cases, mutations involving this gene produce myocytolysis and cardiomyopathy development 50 . In males, the disease develops during adolescence and evolves quickly, but in females it develops later and with a slow progression.…”