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(Pro) gene 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-c oxidase-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 TpsiC stem of the mitochondrial transfer RNA(Pro) gene that segregated with cytochrome-c oxidase 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.