Abstract
Several members of a three-generation kindred from Sardinia were affected by a maternally inherited syndrome characterized by features of both myoclonus epilepsy with ragged-red fibers (MERRF) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Clinically, symptoms such as myoclonus epilepsy, neural deafness and ataxia were variably associated with stroke-like episodes and/or migrainous attacks. Morphologically, numerous ME-LAS-associated SDH-stained vessels were observed in muscle biopsies, either alone or in combination with ragged-red fibers, the morphological hallmark of MERRF. Sequence analysis of the mtDNA tRNA genes revealed the presence of a single, heteroplasmic T → C transition at nt 8356, in the region of the tRNALys gene corrsponding to the T-Ψ-C stem. The T → C(8356) transition was exclusively found in the maternal lineage of our family, and the relative amount of the mutant mtDNA species in muscle was correlated with the severity of the clinical presentation. Therefore, we propose that the T → C(8356) transition is responsible for the mitochondrial encephalomyopathy found in our family, and must be added to the expanding list of the pathogenetically relevant mutations of human mtDNA.
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Acknowledgements
Supported in part by Telethon-Italy and ARIN (As-sociazione Italiana per la promozione delle Ricerche Neurologiche). NS is a Dottorando di Ricerca in Neurosciences at the University of Naples 1 st School of Medicine.
We are indebted to Dr. Marina Mora for expert technical advice.
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Zeviani, M., Muntoni, F., Savarese, N. et al. A MERRF/MELAS Overlap Syndrome Associated with a New Point Mutation in the Mitochondrial DNA tRNALys Gene. Eur J Hum Genet 1, 80–87 (1993). https://doi.org/10.1159/000472390
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DOI: https://doi.org/10.1159/000472390
