A new duplication in the mitochondrially encoded tRNA proline gene in a patient with dilated cardiomyopathy

Abstract

Mitochondria provide an environment conducive to mutations in DNA molecules (mtDNA). Analyses of mtDNA have shown mutations potentially leading to many cardiovascular traits. Here, we describe a patient with dilated cardiomyopathy and new mtDNA duplication. The patient presented symptoms of heart failure New York Heart Association functional class III and was diagnosed with non-familial dilated cardiomyopathy with important left ventricular systolic dysfunction. Sequencing of mtDNA control region was done, and a 15 bp duplication was observed between nucleotides 16,018 and 16,032. Part of this duplication is localized within the tRNA proline gene (tRNA^Pro) that has an important role in cell protection against oxidative stress and is considered an important regulatory factor for cellular reactive oxygen species balance. This duplication could alter the stability or secondary structure of tRNA^Pro, affecting mt-protein synthesis. In turn, the presence of duplication in tRNA^Pro could cause some oxidative stress imbalance and, so, mitochondrial dysfunction could result in the pathogenicity.

Keywords::

• Dilated cardiomyopathy
• genetic duplication
• heart failure
• mitochondrial DNA
• tRNA^Pro gene

Declaration of interest: This study was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, 2010/05317-4) and HC-LIM/FMUSP. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.