The Myoclonic Epilepsy and Ragged-Red Fiber Mutation Provides New Insights into Human Mitochondrial Function and Genetics

Abstract

Of the ~50 mtDNA point mutations, reported so far, that cause disease in humans, ≥ 35 occur in tRNA genes (Schon et al. 1997). Of these, perhaps the best-studied is the A → G transition at position 8344 in the tRNA^(Lys) gene, the mutation that causes myoclonic epilepsy and ragged-red fiber syndrome (MERRF; Shoffner et al. 1990). This disorder is an encephalomyopathy characterized by myoclonic epilepsy, ataxia, and mitochondrial myopathy, with additional dysfunction, in some individuals, in tissues other than brain and skeletal muscle (Schon et al. 1997). Histological analysis of transverse sections of a MERRF patient’s skeletal muscle, stained with Gomori’s modified trichrome stain, reveals the presence of “ragged red fibers,” muscle fibers that exhibit peripheral blotchy, red patches that represent subsarcolemmal accumulations of mitochondria.