A novel mitochondrial DNA deletion producing progressive external ophthalmoplegia associated with multiple sclerosis

Simple item page
dc.contributor.authorSlee, M.
dc.contributor.authorFinkemeyer, J.
dc.contributor.authorKrupa, M.
dc.contributor.authorRaghupathi, R.
dc.contributor.authorGardner, J.
dc.contributor.authorBlumbergs, P.
dc.contributor.authorAgzarian, M.
dc.contributor.authorThyagarajan, D.
dc.date.issued2011
dc.description.abstractWe report a previously undescribed 7676 base pair mitochondrial (mt)DNA deletion involving genes of complex I, complex IV subunits 2 and 3 (cytochrome oxidase [Cox] II, III), adenosine triphosphatase 8 and 6, cytochrome b and 8 transfer (t)RNA genes producing myopathy and progressive external ophthalmoplegia (PEO) in a 44-year-old right-handed Caucasian man with features of multiple sclerosis (MS). We performed complete mtDNA sequencing and deletion analysis, spectrophotometric analysis of muscle and platelet respiratory chain activity, measurement of platelet mitochondrial membrane potential with the potentiometric dye JC-1 and magnetic resonance spectroscopy (MRS) and MRI studies of normal-appearing and lesional cerebral tissue. The deletion resulted in significant respiratory chain deficiency in muscle and blood and abnormalities of the platelet mitochondrial membrane potential. However, cerebrospinal fluid analysis, magnetic resonance spectroscopy and MRI features suggested inflammatory central nervous system demyelination rather than a primary respiratory chain disorder. We conclude that this novel mtDNA deletion causing myopathy and PEO is associated with severe muscle and platelet cellular energetic abnormalities. Furthermore, clinical and paraclinical features of multiple sclerosis were found. The potential pathomechanistic interaction between mtDNA variation and multiple sclerosis is reviewed.
dc.description.statementofresponsibilityM. Slee, J. Finkemeyer, M. Krupa, R. Raghupathi, J. Gardner, P. Blumbergs, M. Agzarian, D. Thyagarajan
dc.identifier.citationJournal of Clinical Neuroscience, 2011; 18(10):1318-1324
dc.identifier.doi10.1016/j.jocn.2011.02.019
dc.identifier.issn0967-5868
dc.identifier.issn1532-2653
dc.identifier.urihttp://hdl.handle.net/2440/68740
dc.language.isoen
dc.publisherChurchill Livingstone
dc.rightsCopyright © 2011 Elsevier Ltd. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.jocn.2011.02.019
dc.subjectMitochondrial disease
dc.subjectMultiple sclerosis
dc.subjectProgressive external ophthalmoplegia
dc.titleA novel mitochondrial DNA deletion producing progressive external ophthalmoplegia associated with multiple sclerosis
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Pathology publications