TY - JOUR
T1 - A novel mitochondrial tRNALeu(UUR) mutation in a patient with features of MERRF and Kearns-Sayre syndrome
AU - Nishigaki, Yutaka
AU - Tadesse, Saba
AU - Bonilla, Eduardo
AU - Shungu, Dikoma
AU - Hersh, Stephen
AU - Keats, Bronya J.B.
AU - Berlin, Charles I.
AU - Goldberg, Morton F.
AU - Vockley, Jerry
AU - DiMauro, Salvatore
AU - Hirano, Michio
PY - 2003/5
Y1 - 2003/5
N2 - 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 tRNALeu(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 tRNALeu(UUR) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.
AB - 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 tRNALeu(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 tRNALeu(UUR) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.
KW - Kearns-Sayre syndrome
KW - Mitochondrial DNA
KW - Mitochondrial encephalomyopathy
KW - Myoclonus epilepsy ragged-red fibers
KW - Point mutation
KW - tRNA
UR - http://www.scopus.com/inward/record.url?scp=0042026576&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042026576&partnerID=8YFLogxK
U2 - 10.1016/S0960-8966(02)00283-3
DO - 10.1016/S0960-8966(02)00283-3
M3 - Article
C2 - 12868503
AN - SCOPUS:0042026576
VL - 13
SP - 334
EP - 340
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 4
ER -