Mutations in mitochondrial tRNA genes: a frequent cause of neuromuscular diseases

Abstract
We have sequenced the tRNA genes of mtDNA from patients with chronic progressive external ophthalmoplegia (CPEO) without detectable mtDNA deletions. Four point mutations were identified, located within highly conserved regions of mitochondrial tRNA genes, namely tRNA Leu(UAG) , tRNA Seu(GCU) , tRNA Gly and tRNA Lys . One of these mutations (tRNA Leu(UAG) ) was found in four patients with different forms of mitochondrial myopathy. An accumulation of three different tRNA point mutations (tRNA Leu(UAG) ), tRNA Seu(GCU) ) and tRNA Gly ) was observed in a single patient, suggesting that mitochondrial tRNA genes represent hotspots for point mutations causing neuromuscular diseases.