MELAS-like encephalomyopathy caused by a new pathogenic mutation in the mitochondrial DNA encoded cytochrome c oxidase subunit I.

TitleMELAS-like encephalomyopathy caused by a new pathogenic mutation in the mitochondrial DNA encoded cytochrome c oxidase subunit I.
Publication TypeJournal Article
Year of Publication2012
AuthorsLamperti, C, Diodato, D, Lamantea, E, Carrara, F, Ghezzi, D, Mereghetti, P, Rizzi, R, Zeviani, M
JournalNeuromuscul Disord
Volume22
Issue11
Pagination990-4
Date Published2012 Nov
ISSN1873-2364
KeywordsCytochrome-c Oxidase Deficiency, Disease Progression, DNA, Mitochondrial, Electron Transport Complex IV, Female, Humans, Magnetic Resonance Imaging, MELAS Syndrome, Muscular Diseases, Mutation, Pedigree, Point Mutation, Protein Subunits, Seizures
Abstract

We report a 35-year-old woman presenting a stroke-like episode with transitory aphasia followed by generalized tonic-clonic seizures. She had severe hearing loss and suffered from frequent episodes of migraine. Although a brain MRI disclosed a T2-hyperintense lesion in the left parietal lobe, she had hardly any long-term sequela. Exercise intolerance, myalgias and limb-girdle muscle weakness indicated a slowly progressive myopathy. Extra-neurological features included short stature, and secondary amenorrhea with low gonadotropin levels, indicating secondary hypogonadism. However, she had three mutation-free, healthy children by ovarian stimulation. A muscle biopsy showed ragged-red, cytochrome c oxidase-negative fibers, and an isolated defect of cytochrome c oxidase activity in muscle mitochondria. Sequence analysis of muscle mtDNA revealed a previously unreported heteroplasmic m.6597C>A transversion in the MTCOI gene, encoding subunit I of cytochrome c oxidase, corresponding to p.Q232K aminoacid change. Analysis on transmitochondrial cybrids demonstrated that the mutation is indeed associated with COX deficiency, i.e. pathogenic.

DOI10.1016/j.nmd.2012.06.003
Alternate JournalNeuromuscul. Disord.
Citation Key10.1016/j.nmd.2012.06.003
PubMed ID22832341
Grant ListGGP11011 / / Telethon / Italy
GPP10005 / / Telethon / Italy