Childhood onset mitochondrial myopathy and lactic acidosis caused by a stop mutation in the mitochondrial cytochrome c oxidase III gene

Horváth, Rita

doi:10.1136/jmg.39.11.812

Cited by 39 publications

(20 citation statements)

References 25 publications

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“…The DNA samples of the study participants were used for carrying out the polymerase chain reaction (PCR) of fragments containing the region of 11 investigated mutations [11][12][13][14][15] .…”

Section: Methodsmentioning

confidence: 99%

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New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations

Sazonova¹,

Рыжкова²,

Sinyov³

et al. 2017

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How to cite this article: Sazonova MA, Ryzhkova AI, Sinyov VV, Galitsyna EV, Orekhova VA, Melnichenko AA, Orekhov AN, Ravani AL, Sobenin IA. New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations. Vessel Plus 2017;1:182-91. Aim:The aim of the present article was the detection of threshold heteroplasmy level of mitochondrial DNA mutations, above which a patient is at increased risk of atherosclerotic lesions. Besides, this parameter was detected for mutations, in which after reaching threshold heteroplasmy level, a protective antiatherogenic effect started to appear. Methods: The participants of the study were 700 women and men from the Moscow region. Fragments of DNA, amplified by polymerase chain reaction, were analyzed with pyrosequencing technology. Then on the basis of pyrograms' peaks in the samples, the heteroplasmy level of the investigated mitochondrial genome mutations was detected. Results: The threshold heteroplasmy level of 11 investigated mutations (m.5178C>A, m.15059G>A, m.652delG, m.13513G>A, m.14846G>A, m.652insG, m.12315G>A, m.3336T>C, m.1555A>G, m.14459G>A, m.3256C>T) in individuals with atherosclerotic plaques or thickening of the intima-medial layer of carotid arteries was detected. Conclusion: Using the method developed in our laboratory, the authors managed to determine threshold heteroplasmy levels of 11 mitochondrial genome mutations associated

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Section: Methodsmentioning

confidence: 99%

“…These mutations often correlate with pathologies which often occur together with atherosclerosis [11][12][13][14][15] . The penetrance of mtDNA mutations depends on the percentage of normal and mutant copies of genome, i.e.…”

Section: Introductionmentioning

confidence: 99%

New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations

Sazonova¹,

Рыжкова²,

Sinyov³

et al. 2017

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“…79 Horvath et al reported a heteroplasmic mutation, 9379GϾA (W58X), generating a premature stop codon in the COIII subunit, in a 6-year-old boy who presented with a relatively mild, slowly progressive myopathy with exercise intolerance, lactic acidosis, growth delay, numerous ragged-red fibers, lipidosis, and severe COX deficiency in skeletal muscle. 41 Although this was a nonsense mutation truncating Ͼ80% of the protein and the mutant load in skeletal muscle was relatively high (93%), this sporadic somatic mutation was absent in the patient's blood or hair follicles, and the patient had only mild myopathy. 41 Encephalomyopathy and multisystem disorders are also clinical features of complex IV defici- ency.…”

Section: Diverse Clinical Spectrum Is Associated With Mutations In Mtmentioning

confidence: 97%

“…41 Although this was a nonsense mutation truncating Ͼ80% of the protein and the mutant load in skeletal muscle was relatively high (93%), this sporadic somatic mutation was absent in the patient's blood or hair follicles, and the patient had only mild myopathy. 41 Encephalomyopathy and multisystem disorders are also clinical features of complex IV defici- ency. 1,15,16,21,40,42,62 A novel heteroplasmic 7587TϾC (M1T in COII) mutation was found in a family with gait ataxia.…”

Section: Diverse Clinical Spectrum Is Associated With Mutations In Mtmentioning

confidence: 97%

“…30,92 The clinical presentations of patients with mutations in mtDNA-encoded COX subunits are arguably the most variable among the phenotypes of RC complex deficiencies caused by mutations in mtDNA-encoded genes ( Table 4). The clinical features vary from the myopathy and exercise intolerance 41,42,46,47,51,79,92 typical of cytochrome b deficiency to severe, early-onset multisystem disease or Leigh syndrome, more typical of complex I and complex V deficiency (Table 4). 15,16,21,114 Although primary respiratory chain dysfunction is a rare cause of rhabdomyolysis, among the 21 mutations in mtDNA complex IV subunit coding regions (excluding the mutation at the termination codon of COI), 5 (5920GϾA, 6708GϾA, 7989TϾC, 9487del15, and 9789TϾC) cause rhabdomyolysis and recurrent myoglobinuria in addition to myopathy and exercise intolerance (Table 2).…”

Section: Diverse Clinical Spectrum Is Associated With Mutations In Mtmentioning

confidence: 99%

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Pathogenic mitochondrial DNA mutations in protein‐coding genes

Wong

2007

Muscle and Nerve

109

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More than 200 disease-related mitochondrial DNA (mtDNA) point mutations have been reported in the Mitomap (http://www.mitomap.org) database. These mutations can be divided into two groups: mutations affecting mitochondrial protein synthesis, including mutations in tRNA and rRNA genes; and mutations in protein-encoding genes (mRNAs). This review focuses on mutations in mitochondrial genes that encode proteins. These mutations are involved in a broad spectrum of human diseases, including a variety of multisystem disorders as well as more tissue-specific diseases such as isolated myopathy and Leber hereditary optic neuropathy (LHON). Because the mitochondrial genome contains a large number of apparently neutral polymorphisms that have little pathogenic significance, along with secondary homoplasmic mutations that do not have primary disease-causing effect, the pathogenic role of all newly discovered mutations must be rigorously established. A scoring system has been applied to evaluate the pathogenicity of the mutations in mtDNA protein-encoding genes and to review the predominant clinical features and the molecular characteristics of mutations in each mtDNA-encoded respiratory chain complex.

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Mitochondrial disorders of the OXPHOS system

2020

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Mitochondrial disorders are amongst the most frequent inborn errors of metabolism, their primary cause being the dysfunction of the oxidative phosphorylation system (OXPHOS). OXPHOS is composed of the electron transport chain (ETC), formed by four multimeric enzymes and two mobile electron carriers, plus an ATP synthase (also called complex V). The ETC performs the redox reactions involved in cellular respiration while generating the proton motive force used by complex V to synthesize ATP. OXPHOS biogenesis involves multiple steps, starting from the expression of genes encoded in physically separated genomes, namely the mitochondrial and nuclear DNA, to the coordinated assembly of components and cofactors building each individual complex and eventually the supercomplexes. The genetic cause underlying around half of the diagnosed mitochondrial disease cases is currently known. Many of these cases result from pathogenic variants in genes encoding structural subunits or additional factors directly involved in the assembly of the ETC complexes. Here we review the historical and most recent findings concerning the clinical phenotypes and the molecular pathological mechanisms underlying this particular group of disorders.

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Childhood onset mitochondrial myopathy and lactic acidosis caused by a stop mutation in the mitochondrial cytochrome c oxidase III gene

Cited by 39 publications

References 25 publications

New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations

New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations

Pathogenic mitochondrial DNA mutations in protein‐coding genes

Mitochondrial disorders of the OXPHOS system

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