A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)

Berardo, Andres; Çoku, Jorida; Kurt, Bulent; DiMauro, Salvatore; Hirano, Michio

doi:10.1016/j.nmd.2010.01.006

« Previous Next »Neuromuscular Disorders
Volume 20, Issue 3 , Pages 204-206, March 2010

A novel mutation in the tRNA^Ile gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)

Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA

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 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.

Keywords: Mitochondrial DNA (mtDNA), Point mutation, tRNA^Ile, Chronic progressive external ophthalmoplegia (CPEO)