ArticleMolecular genetics and metabolism2019
The nuclear background influences the penetrance of the near-homoplasmic m.1630 A > G MELAS variant in a symptomatic proband and asymptomatic mother.
Article in Molecular genetics and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Migratory vasodilatation of cerebral arteries in MELAS episodes: a case report and literature review.Frontiers in immunology · 2026Review
- A rareTranslational pediatrics · 2025Article
- Digenic Inheritance in Rare Disorders and Mitochondrial Disease-Crossing the Frontier to a More Comprehensive Understanding of Etiology.International journal of molecular sciences · 2024Review
- Dysfunctional Postnatal Mitochondrial Energy Metabolism in a Patient with Neurodevelopmental Defects Caused by Intrauterine Growth Restriction Due to Idiopathic Placental Insufficiency.International journal of molecular sciences · 2024Article
- Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Molecular and neurological features of MELAS syndrome in paediatric patients: A case series and review of the literature.Molecular genetics & genomic medicine · 2022Review
- Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS.Molecular omics · 2022Article
- Clinical Insights into Mitochondrial Neurodevelopmental and Neurodegenerative Disorders: Their Biosignatures from Mass Spectrometry-Based Metabolomics.Metabolites · 2021Review
- Applying genomic and transcriptomic advances to mitochondrial medicine.Nature reviews. Neurology · 2021Review
- Genetic and Mitochondrial Metabolic Analyses of an Atypical Form of Leigh Syndrome.Frontiers in cell and developmental biology · 2021Article
- Molecular genetic and mitochondrial metabolic analyses confirm the suspected mitochondrial etiology in a pediatric patient with an atypical form of alternating hemiplegia of childhood.Molecular genetics and metabolism reports · 2020Article
- Response to Bai et al.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Interpretation of mitochondrial tRNA variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Pathophysiology of Conversion to Symptomatic Leber Hereditary Optic Neuropathy and Therapeutic Implications: a Review.Current neurology and neuroscience reports · 2020Review
- Pathogenicity of the m.1630A > G variant remains elusive if related mutation carriers with similar heteroplasmy rates are asymptomatic.Molecular genetics and metabolism reports · 2019Article
- The importance of the nuclear background on the phenotypic signature caused by the MELAS m.1630 A>G variant.Molecular genetics and metabolism reports · 2019Article
- Maternally inherited mitochondrial respiratory disorders: from pathogenetic principles to therapeutic implications.Molecular genetics and metabolismReview
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In this study, we report the metabolic consequences of the m.1630 A > G variant in fibroblasts from the symptomatic proband affected with the mitochondrial encephalomyopathy lactic acidosis and stroke-like episode Syndrome and her asymptomatic mother. By long-range PCR followed by massively parallel sequencing of the mitochondrial genome, we accurately measured heteroplasmy in fibroblasts from the proband (89.6%) and her mother (94.8%). Using complementary experimental approaches, we show a functional correlation between manifestation of clinical symptoms and bioenergetic potential. Our mitochondrial morphometric analysis reveals a link between defects of mitochondrial cristae ultrastructure and symptomatic status. Despite near-homoplasmic level of the m.1630A > G variant, the mother's fibroblasts have a normal OXPHOS metabolism, which stands in contrast to the severely impaired OXPHOS response of the proband's fibroblasts. The proband's fibroblasts also exhibit glycolysis at near constitutive levels resulting in a stunted compensatory glycolytic response to offset the severe OXPHOS defect. Whole exome sequencing reveals the presence of a heterozygous nonsense VARS2 variant (p.R334X) exclusively in the proband, which removes two thirds of the VARS2 protein containing key domains interacting with the mt-tRNA
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.