Myoclonic Epilepsy With Ragged-red Fibers (merrf)
Year: 2015
Type: article
Abstract: , © Sirtoli This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and redistribution in any medium, provided that the original author and source are credited. 1973 saw Tsairis et al. report on case studies within a family where myoclonus epilepsy was associated with ragged-red fibres (RRFs) from muscle tissue biopsies in addition to abnormal blood lactate and pyruvate levels(1). In 1980 Fukuhara N. et al. publish a case study(2) of 2 patients who presented in much the same way as described by Tsairis et al. 7 years ago. Fukuhara et al. entitled their study Myoclonus Epilepsy associated with ragged-red fibres (mitochondrial abnormalities): Disease Entity or a Syndrome? and in so doing, introduced a question highlighting difficulties that the classical 'single disease' medical model encounters when trying to account for overlapping constellations of symptoms. In November of the same year, Wallace et al. come to identify this particular constellation of symptoms by the acronym 'MERRF' following pathophysiological and biochemical characterization of a mitochondrial DNA disease as their study title reports(3). 'Fukuhara's Disease' is another name for it. Soon thereafter in 1981, the human mitochondrial genomes' sequence & organization is published in Nature(4), laying much of the ground work for answering the how's & why's behind Fukuhara et al.'s question. The molecular clue for MERRF was elucidated in 1990 by Shoffner, Wallace et al. who identified a mitochondrial tRNA Lys (mt-tRNA ) point mutation responsible for much of the epilepsy, defective mitochondrial energy production and age-related genotype-phenotype associations observed in MERRF patients(5). The molecular mechanism boils down to defective oxidative phosphorylation (OXPHOS) in the mitochondrial electron transport chain (mETC), caused by faulty protein synthesis originating from a point mutation in the MTTK gene erroneously encoding the highly conserved TѰC loop of its mt-tRNA Lys gene product. This results in aberrant taurine modification, also known as a wobble modification defect [which] is primarily responsible for dispossessing the mutant tRNA Lys of its cognate codon binding affinity, forcing the mutant tRNA UUU to become translationally inactive(6). Nowadays, disorders characterized by defective oxidative phosphorylation are termed 'mitochondrial disorders'(7).
Source: The Winnower
Author: Raphael Sirtoli
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W1191707220