A MERRF/MELAS overlap syndrome associated with a new point mutation in the mitochondrial DNA tRNA(Lys) gene.

TitleA MERRF/MELAS overlap syndrome associated with a new point mutation in the mitochondrial DNA tRNA(Lys) gene.
Publication TypeJournal Article
Year of Publication1993
AuthorsZeviani, M, Muntoni, F, Savarese, N, Serra, G, Tiranti, V, Carrara, F, Mariotti, C, DiDonato, S
JournalEur J Hum Genet
Volume1
Issue1
Pagination80-7
Date Published1993
ISSN1018-4813
KeywordsAcidosis, Lactic, Adolescent, Adult, Ataxia, Base Sequence, Cerebrovascular Disorders, Child, Deafness, DNA, Mitochondrial, Epilepsies, Myoclonic, Female, Humans, Italy, Male, MELAS Syndrome, MERRF Syndrome, Middle Aged, Mitochondrial Myopathies, Molecular Sequence Data, Muscles, Nucleic Acid Conformation, Pedigree, Point Mutation, Polymerase Chain Reaction, RNA, Transfer, Lys
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 MELAS-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 tRNA(Lys) gene corresponding to the T-psi-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.

DOI10.1159/000472390
Alternate JournalEur. J. Hum. Genet.
Citation Key10.1159/000472390
PubMed ID8069654