Severe encephalomyopathy in a patient with homoplasmic A5814G point mutation in mitochondrial tRNA^Cys gene

Abstract

We report a patient with severe encephalomyopathy and homoplasmic A5814G point mutation in the mitochondrial DNA tRNA gene for cysteine. This mutation had been reported in heteroplasmic condition in patients with different clinical phenotypes. Our results confirm the pathogenicity of the mutation and support the concept that homoplasmic mutations in tRNA genes can be responsible for mitochondrial disorders with variable penetrance. This report also extends the clinical spectrum associated with the A5814G mutation.

Introduction

Mitochondrial encephalomyopathies are a heterogeneous group of diseases often associated with multisystemic presentations [1]. The most severely affected organs are those with high oxidative metabolism, such as brain, skeletal and cardiac muscle, and kidney [1]. Diseases due to mutations in mitochondrial DNA (mtDNA) are usually transmitted by maternal inheritance and are heteroplasmic, i.e., mutant and wild-type mtDNAs coexist in tissues.

Since 1988, over 150 point mutations in mitochondrial DNA have been associated with human diseases, many involving mitochondrial tRNA genes [1]. Pathogenic tRNA mutations typically impair mtDNA translation, resulting in disruption of protein synthesis and reduction in the activities of respiratory chain complexes containing mtDNA-encoded polypeptides.

Here, we describe a woman with severe encephalomyopathy and her oligosymptomatic relatives, who harbor an apparently homoplasmic A5814G mutation in the tRNA^Cys gene of mtDNA.