A novel mitochondrial tRNA Arg mutation resulting in an anticodon swap in a patient with mitochondrial encephalomyopathy

• Published in: European journal of human genetics : EJHG Vol. 21; no. 5; pp. 571 - 573
• Main Authors: Roos, Sara, Darin, Niklas, Kollberg, Gittan, Andersson Grönlund, Marita, Tulinius, Mar, Holme, Elisabeth, Moslemi, Ali-Reza, Oldfors, Anders
• Format: Journal Article Magazine Article
• Language: English
• Published: England Nature Publishing Group 01.05.2013
• Subjects: Adolescent; Age; Anticodon - genetics; Anticodons; Ataxia; Base Pairing; Base Sequence; Biochemical analysis; Cataracts; Cell Respiration - physiology; Cytochrome-c oxidase; Cytochrome-c Oxidase Deficiency - genetics; Deoxyribonucleic acid; Disease; DNA; Enzymes; Epithelial cells; Epithelium; Fibroblasts; Genes; Genomes; Genomics; Hair; Histological Techniques; Humans; Male; Mitochondria; Mitochondrial DNA; Mitochondrial Encephalomyopathies - genetics; Mitochondrial Encephalomyopathies - pathology; Molecular Sequence Data; Muscle, Skeletal - pathology; Musculoskeletal system; Mutation; Mutation - genetics; Pediatrics; Pediatrik; Phenotype; Phosphorylation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Restriction fragment length polymorphism; RNA, Transfer, Arg - genetics; Roots; Sequence Analysis, DNA; Short Report; Sweden; tRNA Arg; tRNA Trp; Urine; Sweden
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2012.153

We report a mutation in the anticodon of the tRNA(Arg) gene (m.10437 G>A), resulting in an anticodon swap from GCU to ACU, which is the anticodon of tRNA(Trp), in a boy with mitochondrial encephalomyopathy. Enzyme histochemical analysis of muscle tissue and biochemical analysis of isolated muscle mitochondria demonstrated cytochrome c oxidase (COX) deficiency. Restriction fragment length polymorphism analysis showed that 90% of muscle and 82% of urinary epithelium mtDNA harbored the mutation. The mutation was not identified in blood, fibroblasts, hair roots, or buccal epithelial cells and it was absent in the asymptomatic mother, suggesting that it was a de novo mutation. Single-fiber PCR analysis showed that the proportion of mutated mtDNA correlated with enzyme histochemical COX deficiency. This mutation adds to the three previously described disease-causing mutations in tRNA(Arg), but it is the first mutation occurring in the anticodon of tRNA(Arg).