The A to G transition at nt 3243 of the mitochondrial tRNALeu(UUR) may cause an MERRF syndrome.

Fabrizi, GM; Cardaioli, Elena; Grieco, Gs; Cavallaro, Tiziana; Malandrini, Alessandro; Manneschi, L.; Dotti, Maria Teresa; Federico, Antonio; Guazzi, G. C.

doi:10.1136/jnnp.61.1.47

Cited by 46 publications

(30 citation statements)

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“…2,3,6,7 Atrophy of the brain stem and superior cerebellar peduncles and signal intensity abnormalities of the brain stem were not described. The present study describes these abnormalities in patients with MERRF, and the results are supported by previous neuropathologic studies that showed degeneration of the brain stem and dentate nuclei as well as the basal ganglia, cerebellar cortices, and spinal cord.…”

Section: Discussionmentioning

confidence: 99%

“…The A8344G or A3243G mutations of mitochondrial deoxyribonucleic acid (DNA) are the genetic causative factors. [1][2][3] The clinical phenotype and prognosis are better for patients with the A8344G mutation than for those with the A3243G mutation. 3 Mitochondrial DNA mutation is heteroplasmic, and normal DNA and mutant DNA coexist within the same individual.…”

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confidence: 99%

“…Previous reports have described 1 or more brain MR imaging abnormalities, including cerebral atrophy, cerebral white matter T2 hyperintensities, striatal T2 hyperintensities, pallidal atrophy with calcification, and cerebellar atrophy. 2,3,6,7 Neuropathologic changes include degeneration of the basal ganglia (globus pallidus and substantia nigra), brain stem (pontine tegmentum, locus ceruleus, inferior olivary nucleus, and gracile and cuneate nuclei), cerebellum (dentate nucleus and cerebellar cortex), and spinal cord (posterior columns and spinocerebellar tracts). 8,9 The brain stem and cerebellar degeneration might be the main feature of MERRF, but clinical and MR imaging findings focusing on brain stem and cerebellar abnormalities have not been reported.…”

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Clinical and Brain MR Imaging Features Focusing on the Brain Stem and Cerebellum in Patients with Myoclonic Epilepsy with Ragged-Red Fibers due to Mitochondrial A8344G Mutation

Ito¹,

Shirai²,

Asahina³

et al. 2008

American Journal of Neuroradiology

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SUMMARY:We report 3 patients with myoclonic epilepsy with ragged-red fibers (MERRF) diagnosed by mitochondrial A8344G mutation. Cerebellar ataxia was the first symptom in all patients. Conventional brain MR imaging showed atrophy of the superior cerebellar peduncles and the cerebellum in all patients and brain stem atrophy in 2 patients. In diffusion tensor analysis, fractional anisotropy of the superior cerebellar peduncles was mildly decreased in 1 patient. There was a discrepancy between clinical disabilities (severe) and radiologic abnormalities (mild). This discrepancy and atrophy of the superior cerebellar peduncles and the cerebellum may be important findings suggesting a diagnosis of MERRF. Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial disorder featuring myoclonus, seizures, mental deterioration, cerebellar ataxia, hearing loss, muscular weakness, and other clinical symptoms. The A8344G or A3243G mutations of mitochondrial deoxyribonucleic acid (DNA) are the genetic causative factors.1-3 The clinical phenotype and prognosis are better for patients with the A8344G mutation than for those with the A3243G mutation.3 Mitochondrial DNA mutation is heteroplasmic, and normal DNA and mutant DNA coexist within the same individual.4 Therefore, the onset age and clinical features of MERRF vary, 5 though the onset age is usually adolescence or early adulthood. 6Neuroradiologic findings in patients with MERRF are rarely reported. Previous reports have described 1 or more brain MR imaging abnormalities, including cerebral atrophy, cerebral white matter T2 hyperintensities, striatal T2 hyperintensities, pallidal atrophy with calcification, and cerebellar atrophy. 2,3,6,7 Neuropathologic changes include degeneration of the basal ganglia (globus pallidus and substantia nigra), brain stem (pontine tegmentum, locus ceruleus, inferior olivary nucleus, and gracile and cuneate nuclei), cerebellum (dentate nucleus and cerebellar cortex), and spinal cord (posterior columns and spinocerebellar tracts).8,9 The brain stem and cerebellar degeneration might be the main feature of MERRF, but clinical and MR imaging findings focusing on brain stem and cerebellar abnormalities have not been reported. In the present study, our intent was to clarify the clinical and MR imaging features of patients with MERRF, with particular attention to the brain stem and cerebellum, by using conventional and diffusion tensor MR imaging methods. Case Reports Patient 1A 24-year-old man, who was diagnosed with MERRF with the point mutation of mitochondrial DNA A8344G, initially developed cerebellar symptoms at age 8. He also developed muscular weakness, mental deterioration, myoclonus, and ophthalmoparesis. His brain MR imaging at age 11 revealed slight enlargement of the cerebellar fissures and the fourth ventricle without obvious parenchymal signalintensity abnormalities. His symptoms gradually worsened, and at ages 22 and 24, he underwent 1.5T brain MR imaging including diffusion tensor imaging.Diffusion tensor imaging was p...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Clinical and Brain MR Imaging Features Focusing on the Brain Stem and Cerebellum in Patients with Myoclonic Epilepsy with Ragged-Red Fibers due to Mitochondrial A8344G Mutation

Ito¹,

Shirai²,

Asahina³

et al. 2008

American Journal of Neuroradiology

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“…Thus, patients can have the genetic mutation but be phenotypically normal 13,27,41 or display characteristics of other mtDNA syndromes. 31,[42][43][44] As well, genetic testing is relatively insensitive: patients can have symptomatic mtDNA disorders with negative screen results for common mtDNA mutations. 37,41,45 Presumably these latter patients have either genetic defects not yet described [46][47][48] or genetic defects focused in tissues not used to prepare the mtDNA for the assay.…”

Section: Commentmentioning

confidence: 99%

mtDNA Disease in the Primary Care Setting

Spellberg

Carroll²,

Robinson³

et al. 2001

Archives of Internal Medicine

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Disorders of mitochondrial DNA (mtDNA) may commonly present to primary care physicians but go undiagnosed. A 36-year-old man with a 15-year history of psychosis, seizures, and sensorineural hearing loss and a family history of diabetes mellitus and heart disease presented to our hospital without a unifying diagnosis. Physiologic, biochemical, and genetic testing revealed deficient aerobic metabolism, a defect in mitochondrial electron transport, and the presence of an A-to-G point mutation at position 3243 of the mitochondrial leucine-transfer RNA gene, establishing the diagnosis of mitochondrial encephalopathy, lactic acidosis, and strokelike syndrome (MELAS). Diagnosing mtDNA disorders requires a careful integration of clinical signs and symptoms with pedigree analysis and multidisciplinary testing. Diagnosis is important to provide genetic counseling, avoid unnecessary evaluation, and facilitate therapy for symptomatic relief.

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“…63 The most common mutation observed in MELAS, the A3243G in tRNA Leu(UUR) has also been described in MERRF patients, with no MELAS symptoms. 64,65 Similarly to MELAS, many overlap syndromes have been associated with mt-tRNA mutations like MERRF/MELAS and MELAS/MERRF/Kearns-Sayre. Peculiarly, a MERRF/PEO overlap syndrome associated with the A3243G mutation in tRNA Leu(UUR) has also been described, 66 and a MERRF/Kearns-Sayre syndrome has been associated with the G3255A mutation in tRNA Leu(UUR) .…”

Section: The Clinical Phenotypes Of Mitochondrial Trna Mutationsmentioning

confidence: 99%

Mitochondrial tRNA Mutations: Clinical and Functional Perturbations

Zifa

Giannouli²,

Theotokis³

et al. 2007

RNA Biology

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The A to G transition at nt 3243 of the mitochondrial tRNALeu(UUR) may cause an MERRF syndrome.

Abstract: Objective-To verify the phenotype to genotype correlations of mitochondrial DNA (mtDNA) related disorders in an atypical maternally inherited encephalomyopathy.

Cited by 46 publications

References 16 publications

Clinical and Brain MR Imaging Features Focusing on the Brain Stem and Cerebellum in Patients with Myoclonic Epilepsy with Ragged-Red Fibers due to Mitochondrial A8344G Mutation

Clinical and Brain MR Imaging Features Focusing on the Brain Stem and Cerebellum in Patients with Myoclonic Epilepsy with Ragged-Red Fibers due to Mitochondrial A8344G Mutation

mtDNA Disease in the Primary Care Setting

Mitochondrial tRNA Mutations: Clinical and Functional Perturbations

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