A novel myopathy-associated mitochondrial DNA mutation altering the conserved size of the tRNA(Gln) anticodon loop

We report a novel mitochondrial DNA alteration in a 12-year-old boy with my opathy. We identified a single nucleotide insertion tan adenine) in the mit ochondrial tRNA-glutamine gene. This addition of an additional adenine in a polyadenine stretch (at mitochondrial DNA positions 4366-4369), alters the length of the evolutionary conserved anticodon loop from seven to eight ba ses. The nt-4370 addition was heteroplasmic and was abundant in the patient 's muscle. Lower proportions of mutated mitochondrial DNA were observed in skin fibroblasts. but were below delectable levels in while blood cells. A muscle biopsy of the patient showed ragged red fibers and an unusually high percentage of cytochrome c oxidase-deficient fibers (89%). The pathogenici ty of the mutation was also evident by the fact that fibers harboring lower levels of the mutation showed normal cytochrome c oxidase activity. The in sertion in the anticodon loop of tRNA(Gln) gene identified in our patient m ay provide a unique tool to study protein synthesis in human mitochondria. ( (C) 2000 Elsevier Science B.V. All rights reserved.