Clinical & Experimental Cardiology
Open Access

Abstract

Splice Site Mutation-Induced Alteration of Selective Regional Activity Correlates with the Role of a Gene in Cardiomyopathy

Jia Fei and Shi-You Chen

Splice site mutations of a number of genes are found to induce cardiomyopathy. The mutation alters the thermodynamic activity of nucleotide fragment around the splice sites, which causes exon skipping, leading to dysfunction of certain genes. In the present study, we analyzed the selective and regional characteristic of splice site mutations for genes contributed to the development of cardiomyopathy. 93 splice site mutations in total 16genes involved in cardiomyopathy were analyzed for the information content (Ri). Exon skipping (Ri value<0) appeared to correlate with hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia, the two cardiomyopathies with the highest mortality. We also found that most of the exon skipping was due to the donor splice site mutations instead of the acceptor site mutations at the splice junction. Our studies revealed that the regional preference of mutations at the donor sites is an important factor in determining whether or not the gene plays a role in the development of cardiomyopathies