A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO).
We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI). This is the first mutation at position 44 in the variable loop (V loop) of any mitochondrial tRNA. The muscle biopsy revealed 10% ragged-red/ragged-blue fibers and 25% cytochrome c oxidase (COX)-deficient fibers. No deletions or duplications were detected by Southern blot analysis. The 4302A>G transition was present only in the patient's muscle and single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient than in normal fibers. Like tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing CPEO.
Berardo
Andres
A
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
Coku
Jorida
J
Kurt
Bulent
B
DiMauro
Salvatore
S
Hirano
Michio
M
D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology; D012355:RNA, Transfer, Ile / Q000235:genetics*
D004272:DNA, Mitochondrial; D012355:RNA, Transfer, Ile; D003576:Electron Transport Complex IV