A New Mitochondrial Transfer RNAPro Gene Mutation Associated With Myoclonic Epilepsy With Ragged-Red Fibers and Other Neurological Features

Background

Pathogenic mutations of the human mitochondrial genome are associated with well-characterized, progressive neurological syndromes, with mutations in the transfer RNA genes being particularly prominent.

Objective

To describe a novel mitochondrial transfer RNA^Progene mutation in a woman with a myoclonic epilepsy with ragged-red fibers–like disease.

Design, Setting, and Patient

Case report of a 49-year-old woman presenting with a myoclonic epilepsy with ragged-red fibers–like disease comprising myoclonic jerks, cerebellar ataxia, and proximal muscle weakness.

Results

Histochemical analysis of a muscle biopsy revealed numerous cytochrome-coxidase–deficient, ragged-red fibers, while biochemical studies indicated decreased activity of respiratory chain complex I. Molecular investigation of mitochondrial DNA revealed a new heteroplasmic mutation in the TψC stem of the mitochondrial transfer RNA^Progene that segregated with cytochrome-coxidase deficiency in single muscle fibers.

Conclusions

Our case serves to illustrate the ever-evolving phenotypic spectrum of mitochondrial DNA disease and the importance of performing comprehensive mitochondrial genetic studies in the absence of common mitochondrial DNA mutations.