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Ryoikibetsu Shokogun Shirizu 2002
Review
Topics: DNA, Mitochondrial; Diagnosis, Differential; Humans; MERRF Syndrome; Point Mutation; RNA; RNA, Mitochondrial; RNA, Transfer, Lys
PubMed: 12483877
DOI: No ID Found -
Journal of Clinical Medicine Nov 2021Mitochondrial disorders are a remarkably complex group of diseases caused by impairment of the mitochondrial respiratory chain (or electron transport chain) [...].
Mitochondrial disorders are a remarkably complex group of diseases caused by impairment of the mitochondrial respiratory chain (or electron transport chain) [...].
PubMed: 34830516
DOI: 10.3390/jcm10225235 -
Metabolic Brain Disease Mar 2014We report the case of a 19-year-old Chinese female harboring the m.3291T>C mutation in the MT-TL1 gene encoding the mitochondrial transfer RNA for leucine. She presented...
We report the case of a 19-year-old Chinese female harboring the m.3291T>C mutation in the MT-TL1 gene encoding the mitochondrial transfer RNA for leucine. She presented with a complex phenotype characterized by progressive cerebellar ataxia, frequent myoclonus seizures, recurrent stroke-like episodes, migraine-like headaches with nausea and vomiting, and elevated resting lactate blood level. It is known that the myoclonus epilepsy with ragged-red fibers (MERRF) is characterized by cerebellar ataxia and myoclonus epilepsy, while that the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by recurrent stroke-like episodes, migraine-like headaches, and elevated resting lactate blood level. So the patient's clinical manifestations suggest the presence of a MERRF/MELAS overlap syndrome. Muscle biopsy of the patient showed the presence of numerous scattered ragged-red fibers, some cytochrome c oxidase-deficient fibers, and several strongly succinate dehygrogenase-reactive vessels, suggestive of a mitochondrial disorder. Direct sequencing of the complete mitochondrial genome of the proband revealed no mutations other than the T-to-C transition at nucleotide position 3291. Restriction fragment length polymorphism analysis of the proband and her family revealed maternal inheritance of the mutation in a heteroplasmic manner. The analysis of aerobic respiration and glycolysis demonstrated that the fibroblasts from the patient had mitochondrial dysfunction. Our results suggest that the m.3291T>C is pathogenic. This study is the first to describe the m.3291T>C mutation in association with the MERRF/MELAS overlap syndrome.
Topics: Atrophy; Brain; Cells, Cultured; Child, Preschool; DNA, Mitochondrial; Electroencephalography; Electron Transport; Extracellular Fluid; Female; Fibroblasts; Glycolysis; Humans; Hydrogen-Ion Concentration; MELAS Syndrome; MERRF Syndrome; Magnetic Resonance Imaging; Middle Aged; Muscle Fibers, Slow-Twitch; Neurologic Examination; Oxygen Consumption; Point Mutation; RNA, Transfer, Leu; Young Adult
PubMed: 24338029
DOI: 10.1007/s11011-013-9464-5 -
Seizure Jun 2012Information about epilepsy in mitochondrial disorders is scarce although a number or syndromic and non-syndromic mitochondrial disorders frequently manifest with focal... (Review)
Review
OBJECTIVES
Information about epilepsy in mitochondrial disorders is scarce although a number or syndromic and non-syndromic mitochondrial disorders frequently manifest with focal or generalized seizures. Aim of the review was to describe epilepsy in syndromic and non-syndromic mitochondrial disorders with epilepsy as a dominant or collateral feature of the phenotype.
METHODS
Literature search via Pubmed using the key words "mitochondrial", "epilepsy", "seizures", and all acronyms of syndromic mitochondrial disorders.
RESULTS
Syndromic mitochondrial disorders obligatory associated with epilepsy include Alpers-Huttenlocher-syndrome (AHS), ataxia neuropathy spectrum (ANS), Leigh-syndrome, MELAS-syndrome, myoclonic epilepsy, myopathy, and sensory ataxia (MEMSA) syndrome, and MERRF-syndrome, Occasionally, epilepsy is a phenotypic feature in IOSCA, KSS, LHON, LBSL, or NARP, All types of seizures occur but most frequently generalized tonic-clonic seizures, partial seizures, myoclonic jerks, or West-syndrome was reported. Treatment of epilepsy in patients with mitochondrial disorders is not at variance from epilepsy of other causes but mitochondrion-toxicity of various antiepileptic drugs, such as valproic acid, carbamazepine etc. has to be considered to avoid severe complications or deterioration of the underlying disease.
CONCLUSIONS
Epilepsy is a common phenotypic feature of syndromic as well as non-syndromic mitochondrial disorders. Treatment of epilepsy in mitochondrial disorders is not at variance from treatment of epilepsy due to other causes but mitochondrion-toxic drugs should be avoided.
Topics: Anticonvulsants; Ataxia; Epilepsy; Humans; Mitochondrial Diseases; Mutation; Phenotype
PubMed: 22459315
DOI: 10.1016/j.seizure.2012.03.003 -
Scientific Reports Mar 2016Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a mitochondrial disorder characterized by myoclonus epilepsy, generalized seizures, ataxia and myopathy....
Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a mitochondrial disorder characterized by myoclonus epilepsy, generalized seizures, ataxia and myopathy. MERRF syndrome is primarily due to an A to G mutation at mtDNA 8344 that disrupts the mitochondrial gene for tRNA(Lys). However, the detailed mechanism by which this tRNA(Lys) mutation causes mitochondrial dysfunction in cardiomyocytes or neurons remains unclear. In this study, we generated human induced pluripotent stem cells (hiPSCs) that carry the A8344G genetic mutation from patients with MERRF syndrome. Compared with mutation-free isogenic hiPSCs, MERRF-specific hiPSCs (MERRF-hiPSCs) exhibited reduced oxygen consumption, elevated reactive oxygen species (ROS) production, reduced growth, and fragmented mitochondrial morphology. We sought to investigate the induction ability and mitochondrial function of cardiomyocyte-like cells differentiated from MERRF-hiPSCs. Our data demonstrate that that cardiomyocyte-like cells (MERRF-CMs) or neural progenitor cells (MERRF-NPCs) differentiated from MERRF-iPSCs also exhibited increased ROS levels and altered antioxidant gene expression. Furthermore, MERRF-CMs or -NPCs contained fragmented mitochondria, as evidenced by MitoTracker Red staining and transmission electron microscopy. Taken together, these findings showed that MERRF-hiPSCs and MERRF-CM or -NPC harboring the A8344G genetic mutation displayed contained mitochondria with an abnormal ultrastructure, produced increased ROS levels, and expressed upregulated antioxidant genes.
Topics: Adolescent; Cell Dedifferentiation; Cell Differentiation; Cells, Cultured; DNA, Mitochondrial; Female; Humans; Induced Pluripotent Stem Cells; MERRF Syndrome; Mitochondria, Heart; Myocytes, Cardiac; Organelle Shape; Oxygen Consumption; Point Mutation; Reactive Oxygen Species
PubMed: 27025901
DOI: 10.1038/srep23661 -
Muscle & Nerve Apr 1995
Topics: Humans; MERRF Syndrome; Restless Legs Syndrome; Terminology as Topic
PubMed: 7715638
DOI: 10.1002/mus.880180420 -
Internal Medicine (Tokyo, Japan) 2010Myoclonic epilepsy with ragged red fibers (MERRF), also called Fukuhara's disease, is sometimes accompanied by the rare symptom of multiple symmetric lipomatosis (MSL)....
Myoclonic epilepsy with ragged red fibers (MERRF), also called Fukuhara's disease, is sometimes accompanied by the rare symptom of multiple symmetric lipomatosis (MSL). MSL associated with MERRF has been reported mainly in Caucasians; such cases have not been reported in Japanese patients. We report the case of a 59-year-old Japanese woman with MERRF syndrome associated with A-->G substitution at nucleotide 8,344 of mtDNA. This case suggests that differences in lifestyle and gene polymorphism among races may be related to the prevalence of MSL due to mitochondrial abnormality, and that mitochondrial abnormalities should be considered as a cause of MSL even in Japanese patients.
Topics: DNA, Mitochondrial; Female; Humans; Japan; Lipomatosis, Multiple Symmetrical; MERRF Syndrome; Middle Aged; Mitochondria, Muscle
PubMed: 20190488
DOI: 10.2169/internalmedicine.49.2996 -
Amino Acids Jan 2014Taurine is an abundant β-amino acid that concentrates in the mitochondria, where it participates in the conjugation of tRNAs for leucine, lysine, glutamate and... (Review)
Review
Taurine is an abundant β-amino acid that concentrates in the mitochondria, where it participates in the conjugation of tRNAs for leucine, lysine, glutamate and glutamine. The formation of 5-taurinomethyluridine-tRNA strengthens the interaction of the anticodon with the codon, thereby promoting the decoding of several codons, including those for AAG, UUG, CAG and GAG. By preventing these series of events, taurine deficiency appears to diminish the formation of 5-taurinomethyluridine and causes inefficient decoding for the mitochondrial codons of leucine, lysine, glutamate and glutamine. The resulting reduction in the biosynthesis of mitochondria-encoded proteins deprives the respiratory chain of subunits required for the assembly of respiratory chain complexes. Hence, taurine deficiency is associated with a reduction in oxygen consumption, an elevation in glycolysis and lactate production and a decline in ATP production. A similar sequence of events takes place in mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fiber syndrome). In both diseases, mutations in their respective tRNAs interfere with the formation of 5-taurinomethyluridine in the wobble position. Hence, the taurine-deficient phenotype resembles the phenotypes of MELAS and MERRF.
Topics: Animals; Codon, Terminator; Electron Transport; Glycolysis; Humans; MERRF Syndrome; Mitochondria; Mitochondrial Myopathies; Mitochondrial Proteins; RNA, Transfer; Taurine; Uridine
PubMed: 23179085
DOI: 10.1007/s00726-012-1414-8 -
Acta Neurologica Scandinavica Jun 1993We describe a 42-year-old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF...
We describe a 42-year-old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonus epilepsy and ragged-red fibers). Clinically, she had episodic headache, stroke-like episode with left hemiparesis and lactic acidosis commonly found in MELAS syndrome. However, myoclonus seizure, and ataxia with dyssynergic gait characteristic of MERRF were also noted. Computed tomographic scans showed a right temporo-parietal hypodense lesion. The lesion disappeared 20 months later, even magnetic resonance images also failed to reveal this abnormality. A molecular analysis of mitochondrial DNA was conducted by using restriction endonucleases ApaI and NaeI. A transition from A to G was found at the nucleotide position 3243, but not found at the 8344th nucleotide pair. In this report, we document the fluctuating CT changes and emphasize the importance of molecular analysis in patients with overlapping syndrome of mitochondrial encephalomyopathies.
Topics: Adult; Base Composition; Biopsy; Brain; DNA, Mitochondrial; Diagnosis, Differential; Female; Humans; MERRF Syndrome; Magnetic Resonance Imaging; Muscles; Neurologic Examination; Point Mutation; Polymerase Chain Reaction; Tomography, X-Ray Computed
PubMed: 8356881
DOI: 10.1111/j.1600-0404.1993.tb04143.x -
Muscle & Nerve Sep 2011A 48-year-old man presented with a complex phenotype of myoclonus epilepsy with ragged-red fibers (MERRF) syndrome and Kearns-Sayre syndrome (KSS), which included...
A 48-year-old man presented with a complex phenotype of myoclonus epilepsy with ragged-red fibers (MERRF) syndrome and Kearns-Sayre syndrome (KSS), which included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy, bifascicular heart block, and ragged-red fibers. The m.3291T>C mutation in the tRNA(Leu(UUR)) gene was found with 92% heteroplasmy in muscle. This mutation has been reported with MELAS, myopathy, and deafness with cognitive impairment. This is the first description with a MERRF/KSS syndrome.
Topics: Biopsy; Cerebellar Ataxia; Comorbidity; DNA, Mitochondrial; Electrocardiography; Epilepsies, Myoclonic; Hearing Loss; Humans; Kearns-Sayre Syndrome; MERRF Syndrome; Male; Middle Aged; Muscle Weakness; Mutation; Quadriceps Muscle
PubMed: 21996807
DOI: 10.1002/mus.22149