The 8,344 mutation in mitochondrial DNA: A comparison between the proportion of mutant DNA and clinico-pathologic findings

Ozawa, Matsuko; Goto, Yu‐ichi; Sakuta, Ryoichi; Tanno, Y; Tsuji, Shoji; Nonaka, Ikuya

doi:10.1016/0960-8966(95)00009-c

Cited by 32 publications

(34 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some of these clinical findings may be absent in the early stage of the disease, while in advanced disease patients usually have more uniform clinical manifestations 22,24,27,28 . A clinical follow-up scheme was recently reported by Mancuso et al for patients with the A8344G mutation ( Table 2) 28 .…”

Section: What Are the Clinical Features?mentioning

confidence: 99%

“…Complexes I and IV seem to be more involved in the respiratory chain in patients with MERRF, and they are usually associated with changes in other respiratory chain complexes, whereas complex II seems to be the least affected 8,23,27,34,42,43,44 . The number of muscle fibers with deficient activity of COX observed upon muscle biopsy suggests that respiratory chain complex IV could be one of the complexes that are most affected in MERRF patients 45,46,47,48,49,50,51,52,53,54,55,56,57 .…”

Section: What Are the Laboratory And Biochemical Features?mentioning

confidence: 99%

“…The lactic acid level in the blood and cerebrospinal fluid (CSF) is elevated at rest in patients with MERFF and can increase moderately after physical activity 4,27 . These high lactic acid serum levels can also be found in the asymptomatic family members of patients with MERRF 24 .…”

Section: What Are the Laboratory And Biochemical Features?mentioning

confidence: 99%

“…Cerebellar ataxia is one of the most common clinical manifestations of MERRF and is supportive of the diagnostic criteria of MERRF, occurring in up to 83% of cases 6,35 . The presence of manifestation cerebellar ataxia is an important indicator in patients with MERRF, although it may not be present in the early phase of the disease 27,34 . However, clinical and radiological findings in patients with MERRF vary and may suggest spinocerebellar degeneration, especially in early phase of the disease 36 .…”

Section: What Are the Clinical Features?mentioning

confidence: 99%

See 3 more Smart Citations

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Lorenzoni

Scola

Kay

et al. 2014

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Myoclonic epilepsy associated with ragged red fibers (MERRF) is a rare mitochondrial disorder. Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. Clinical features of MERRF are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNA Lys gene of the DNAmt, mainly A8344G, are responsible for almost 90% of MERRF cases. Morphological changes seen upon muscle biopsy in MERRF include a substantive proportion of RRF, muscle fibers showing a deficient activity of cytochrome c oxidase (COX) and the presence of vessels with a strong reaction for succinate dehydrogenase and COX deficiency. In this review, we discuss mainly clinical and laboratory manifestations, brain images, electrophysiological patterns, histology and molecular findings as well as some differential diagnoses and treatments.Keywords: MERRF, mitochondrial, epilepsy, myoclonus, myopathy. RESUMOEpilepsia mioclônica associada com fibras vermelhas rasgadas (MERRF) é uma rara doença mitocondrial. O critério diagnóstico para MERRF inclui as manifestações típicas da doença: mioclonia, epilepsia generalizada, ataxia cerebelar e fibras vermelhas rasgadas (RRF) na biópsia de músculo. Na fase inicial da doença, as manifestações clínicas podem não ser uniformes, e correlação entre as manifestações clínicas e fisiopatologia não estão completamente elucidadas. Estima-se que as mutações de ponto no gene tRNA Lys do DNAmt, principalmente a A8344G, sejam responsáveis por quase 90% dos casos de MERRF. As alterações morfológicas na biópsia muscular incluem uma grande proporção de RRF, fibras musculares com deficiência de atividade da citocromo c oxidase (COX) e presença de vasos com forte reação para succinato desidrogenase e deficiência da COX. Nesta revisão, são discutidas as principais manifestações clínicas e laboratoriais, imagens cerebrais, padrões eletrofisiológicos, histológicos e alterações moleculares, bem como, alguns dos diagnósticos diferenciais e tratamentos.

show abstract

Section: What Are the Clinical Features?mentioning

confidence: 99%

Section: What Are the Laboratory And Biochemical Features?mentioning

confidence: 99%

Section: What Are the Laboratory And Biochemical Features?mentioning

confidence: 99%

Section: What Are the Clinical Features?mentioning

confidence: 99%

See 2 more Smart Citations

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Lorenzoni

Scola

Kay

et al. 2014

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

show abstract

“…Additional clinical manifestations can include short stature, hearing loss, pigmentary retinopathy, optic atrophy, dementia, peripheral neuropathy, cardiomyopathy, or renal tubular dysfunction [3,4]. Lactate and pyruvate are commonly elevated in serum at rest and increase excessively after moderate physical activities [5]. The m.8344A>G mutation in the mtDNA gene MT-TK, which encodes mitochondrial transfer (t)RNA Lysine is the most common mutation asso< ciated with MERRF syndrome, although other mutations in tRNA Lysine or genes encoding different tRNAs have been identified in MERRF patients [6,7].…”

Section: Introductionmentioning

confidence: 99%

Recovery of MERRF Fibroblasts and Cybrids Pathophysiology by Coenzyme Q10

et al. 2012

View full text Add to dashboard Cite

Mitochondrial DNA mutations are an important cause of human disease for which there is no effective treatment. Myoclonic epilepsy with ragged-red fibers (MERRF) is a mitochondrial disease usually caused by point mutations in transfer RNA genes encoded by mitochondrial DNA. The most common mutation associated with MERRF syndrome, m.8344A>G in the gene MT-TK, which encodes transfer RNA Lysine , affects the translation of all mitochondrial DNA encoded proteins. This impairs the assembly of the electron transport chain complexes leading to decreased mitochondrial respiratory function. Here we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from patients harboring the A8344G mutation. Coenzyme Q 10 (CoQ) levels, as well as mitochondrial respiratory chain activity, and mitochondrial protein expression levels were significantly decreased in MERRF fibroblasts. Mitotracker staining and imaging analysis of individual mitochondria indicated the presence of small, rounded, depolarized mitochondria in MERRF fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and increased degradation of impaired mitochondria by mitophagy. Transmitochondrial cybrids harboring the A8344G mutation also showed CoQ deficiency, mitochondrial dysfunction, and increased mitophagy activity. All these abnormalities in patient-derived fibroblasts and cybrids were partially restored by CoQ supplementation, indicating that these cell culture models may be suitable for screening and validation of novel drug candidates for MERRF disease.

show abstract

Muscle Phenotype and Mutation Load in 51 Persons With the 3243A>G Mitochondrial DNA Mutation

Jeppesen¹,

Schwartz²,

Frederiksen³

et al. 2006

Arch Neurol

View full text Add to dashboard Cite

show abstract

The 8,344 mutation in mitochondrial DNA: A comparison between the proportion of mutant DNA and clinico-pathologic findings

Cited by 32 publications

References 17 publications

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Recovery of MERRF Fibroblasts and Cybrids Pathophysiology by Coenzyme Q10

Muscle Phenotype and Mutation Load in 51 Persons With the 3243A>G Mitochondrial DNA Mutation

Contact Info

Product

Resources

About