ArticleBrain : a journal of neurology2012
Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.
Article in Brain : a journal of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 97 citations in OpenAlex.
- Targeted long-read sequencing enables comprehensive analysis of the genetic and epigenetic landscape of inherited myopathies.Nature communications · 2026Article
- Amyotrophic Lateral Sclerosis With Concurrent LHON-associated m.14484T>C Mutation: A Case Report and Literature Review.Revista de neurologia · 2025Review
- Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Mitochondrial DNA Mutations and Epigenetic Regulation in Type 2 Diabetes Mellitus Development.British journal of biomedical science · 2025Review
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Deoxyguanosine kinase deficiency: natural history and liver transplant outcome.Brain communications · 2024Article
- Progressive external ophthalmoplegia.Handbook of clinical neurology · 2023Review
- Prominent muscle involvement in a familial form of mitochondrial disease due to aFrontiers in genetics · 2023Article
- Case report: NovelFrontiers in pediatrics · 2023Article
- Methods to improve the accuracy of next-generation sequencing.Frontiers in bioengineering and biotechnology · 2023Review
- Molecular Genetics Overview of Primary Mitochondrial Myopathies.Journal of clinical medicine · 2022Review
- Case Report: Rare HomozygousFrontiers in genetics · 2022Article
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance.Clinical genetics · 2020Article
- Identification of protein targets for the antidepressant effects ofNeural regeneration research · 2020Article
- Article
- Mitoepigenetics and Its Emerging Roles in Cancer.Frontiers in cell and developmental biology · 2020Review
- SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications.Frontiers in neurology · 2020Review
- Mitochondrial diseases: expanding the diagnosis in the era of genetic testing.Journal of translational genetics and genomics · 2020Article
- Mitochondrial myopathy plus due to the variant m.586G > A in MT-TF.Molecular genetics and metabolism reports · 2019Article
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17 authors at 3 institutions in 2 countries.
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Abstract
The molecular diagnosis of mitochondrial disorders still remains elusive in a large proportion of patients, but advances in next generation sequencing are significantly improving our chances to detect mutations even in sporadic patients. Syndromes associated with mitochondrial DNA multiple deletions are caused by different molecular defects resulting in a wide spectrum of predominantly adult-onset clinical presentations, ranging from progressive external ophthalmoplegia to multi-systemic disorders of variable severity. The mutations underlying these conditions remain undisclosed in half of the affected subjects. We applied next-generation sequencing of known mitochondrial targets (MitoExome) to probands presenting with adult-onset mitochondrial myopathy and harbouring mitochondrial DNA multiple deletions in skeletal muscle. We identified autosomal recessive mutations in the DGUOK gene (encoding mitochondrial deoxyguanosine kinase), which has previously been associated with an infantile hepatocerebral form of mitochondrial DNA depletion. Mutations in DGUOK occurred in five independent subjects, representing 5.6% of our cohort of patients with mitochondrial DNA multiple deletions, and impaired both muscle DGUOK activity and protein stability. Clinical presentations were variable, including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis in a young female who had received a liver transplant at 9 months of age and adult-onset lower motor neuron syndrome with mild cognitive impairment. These findings reinforce the concept that mutations in genes involved in deoxyribonucleotide metabolism can cause diverse clinical phenotypes and suggest that DGUOK should be screened in patients harbouring mitochondrial DNA deletions in skeletal muscle.
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