Chronic Progressive External Ophthalmoplegia due to a Rare de novo m.12334G>A MT-TL2 Mitochondrial DNA Variant1

J Neuromuscul Dis. 2020;7(3):355-360. doi: 10.3233/JND-200486.


We describe a patient with chronic progressive external ophthalmoplegia (CPEO) due to a rare mitochondrial genetic variant. Muscle biopsy revealed numerous cytochrome c oxidase (COX)-deficient fibres, prompting sequencing of the entire mitochondrial genome in muscle which revealed a rare m.12334G>A variant in the mitochondrial (mt-) tRNALeu(CUN)(MT-TL2) gene. Analysis of several tissues showed this to be a de novo mutational event. Single fibre studies confirmed the segregation of high m.12334G>A heteroplasmy levels with the COX histochemical defect, confirming pathogenicity of the m.12334G>A MT-TL2 variant. This case illustrates the importance of pursuing molecular genetic analysis in clinically-affected tissues when mitochondrial disease is suspected.

Keywords: CPEO; Chronic progressive external ophthalmoplegia; cytochrome c oxidase; mitochondrial DNA.

Publication types

  • Case Reports

MeSH terms

  • Cytochrome-c Oxidase Deficiency / genetics*
  • DNA, Mitochondrial / genetics*
  • Humans
  • Ophthalmoplegia, Chronic Progressive External / genetics*
  • RNA, Transfer, Leu / genetics*


  • DNA, Mitochondrial
  • RNA, Transfer, Leu