A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)
Received 12 August 2009; received in revised form 14 December 2009; accepted 14 January 2010.
Abstract
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 tRNAIle 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 tRNALeu(UUR), tRNAIle appears to be a “hot spot” for mtDNA mutations causing CPEO.
ABSTRACT