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Mariarosa A. B. Melone, MD; Alessandra Tessa, PhD; Stefania Petrini, PhD; Giacomo Lus, MD; Simone Sampaolo, MD; Giuseppe di Fede, MD; Filippo M. Santorelli, MD; Roberto Cotrufo, MD

Arch Neurol. 2004;61:269-272.

Background  A 26-year-old man presented at onset with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and later with a phenotype for MELAS and myoclonic epilepsy and ragged red fiber disease (MELAS/MERRF).

Objective  To identify the possible defects in the mitochondrial genome in blood and muscle samples of the patient.

Design  Case study of a patient clinically exhibiting strokelike episodes and then epilepsy with myoclonic features, ataxia, and dementia.

Setting  Research unit of a university hospital.

Main Outcome Measures  Electromyographic, morphologic, and biochemical studies of muscle and molecular analysis of blood and muscle to investigate mitochondrial DNA (mtDNA) size and quantity.

Results  Morphologically, we found abnormal mitochondrial proliferation with several cytochrome-c oxidase (COX)–negative fibers in muscle biopsy specimens; the analysis of serial sections showed a decreased immunoreactivity for the mtDNA-encoded subunits COXII and, partially, COXI. Biochemically, we found a partial and isolated COX deficiency. The complete mtDNA sequence analysis identified 3 sequence changes, 2 of which were reported polymorphisms. The remaining change, a G12147A transition in the transfer RNA^His gene, appeared to be the likely pathogenic mutation.

Conclusions  Our data propose that the G12147A change, the first mutation in the transfer RNA^His gene associated with an overlapped MELAS/MERFF phenotype, is the cause of the encephalomyopathy in this patient interfering with the overall mitochondrial protein synthesis.

From the First Division of Neurology, Department of Neurological Sciences, Second University of Naples, Naples, Italy (Drs Melone, Lus, Sampaolo, di Fede, and Cotrufo); and the Department of Molecular Medicine, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS)–Bambino Gesù (Drs Tessa, Petrini, and Santorelli), Rome, Italy.

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