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

Publication Type	Case Report
Authors	Nishigaki Y, Tadesse S, Bonilla E, Shungu D, Hersh S, Keats B, Berlin C, Goldberg M, Vockley J, DiMauro S, Hirano M
Journal	Neuromuscul Disord
Volume	13
Issue	4
Pagination	334-40
Date Published	05/01/2003
ISSN	0960-8966
Keywords	DNA, Mitochondrial, Kearns-Sayre Syndrome, MERRF Syndrome, Mutation, RNA, RNA, Transfer, Leu
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.
DOI	10.1016/s0960-8966(02)00283-3
PubMed ID	12868503