title: MERRF/MELAS overlap syndrome due to the m.3291T>C mutation.
abstract: 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.
authors: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors: Kaiming
authors: K
authors: Liu
authors: Hui
authors: H
authors: Zhao
authors: Kunqian
authors: K
authors: Ji
authors: Chuanzhu
authors: C
authors: Yan
mesh_terms: D001284:Atrophy; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D004569:Electroencephalography; D004579:Electron Transport; D045604:Extracellular Fluid / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology; D017243:MERRF Syndrome / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D018657:Muscle Fibers, Slow-Twitch / Q000473:pathology; D009460:Neurologic Examination; D010101:Oxygen Consumption; D017354:Point Mutation; D012356:RNA, Transfer, Leu / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu