Affiliations: [a] Department of Neurology, Tallaght University Hospital, Tallaght, Dublin, Ireland
| [b] Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| [c] NHS Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
| [d] Department of Neurophysiology, Tallaght University Hospital, Tallaght, Dublin, Ireland
| [e] Academic Unit of Neurology, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| [f] Department of Neurology, Belfast Health and Social Care Trust, Belfast, United Kingdom
| [g] Department of Neurology, Hermitage Medical Clinic, Dublin, Ireland
| [h] Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
Correspondence to: Dr. Luke O’Donnell, Department of Neurology, Tallaght University Hospital, Tallaght, Dublin 24. Tel.: +353872819220; E-mail: [email protected].
Note:  Submission of data to a genetic database: We have submitted the above variant to the database MSeqDR: the Mitochondrial Disease Sequence Data Resource Consortium. Available from: https://mseqdr.org/variant.php?variant=MSCV_0005629.
Abstract: 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.