A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome.

Abstract

In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and Kearns-Sayre syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial DNA (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNA(Leu(UUR)) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I + III, II + III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts (< 2%). The mutation was absent in 50 control DNA samples. Single-fiber analysis revealed a higher proportion of mutation in COX-deficient RRF (94% +/- 5, n = 25) compared to COX-positive non-RRF (18% +/- 9, n = 21). The identification of yet another tRNA(Leu(UUR)) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.

• Authors: Yutaka Nishigaki, Saba Tadesse, Eduardo Bonilla, Dikoma Shungu, Stephen Hersh, Bronya J B Keats, Charles I Berlin, Morton F Goldberg, Jerry Vockley, Salvatore DiMauro, Michio Hirano
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 13 Issue 4 Pg. 334-40 (May 2003) ISSN: 0960-8966 [Print] England
• PMID: 12868503 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Mitochondrial
• RNA, Mitochondrial
• RNA, Transfer, Leu
• Guanine
• RNA
• Electron Transport Complex IV
• Adenine

Topics

• Adenine (metabolism)
• Adult
• Animals
• Base Sequence
• DNA, Mitochondrial (metabolism)
• Electron Transport Complex IV (genetics, metabolism)
• Guanine (metabolism)
• Humans
• Kearns-Sayre Syndrome (genetics)
• MERRF Syndrome (genetics)
• Male
• Mitochondria, Muscle (metabolism, pathology)
• Molecular Sequence Data
• Muscle Fibers, Skeletal (metabolism, pathology)
• Muscle, Skeletal (metabolism, pathology)
• Mutation
• Polymerase Chain Reaction
• RNA (metabolism)
• RNA, Mitochondrial
• RNA, Transfer, Leu (metabolism)