ArticleHuman molecular genetics2017
A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Model systems informing mechanisms and drug discovery: a review ofWellcome open research · 2023Pooled it
- Model organisms in POLG-related disorders: insights from yeast to multicellular systems.Cell death & disease · 2025Review
- Preventing excessive autophagy protects from the pathology of mtDNA mutations in Drosophila melanogaster.Nature communications · 2024Article
- Molecular diagnosis of patients with syndromic short stature identified by trio whole-exome sequencing.Frontiers in genetics · 2024Article
- Mitochondrial DNA-targeted therapy: A novel approach to combat cancer.Cell insight · 2023Review
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions.Molecular genetics & genomic medicine · 2022Article
- Mutations of mitochondrial DNA are not major contributors to aging of fruit flies.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the mitochondrial DNA polymerase, POLG, are associated with a variety of clinical presentations, ranging from early onset fatal brain disease in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity and maintenance. On a molecular level, depending on their location within the enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple mtDNA deletions, and in some cases these molecular changes can be correlated to the clinical presentation. We identified a patient with a dominant p.Y955H mutation in POLG, presenting with a severe, early-onset multi-systemic mitochondrial disease with bilateral sensorineural hearing loss, cataract, myopathy, and liver failure. Using a combination of disease models of Drosophila melanogaster and in vitro biochemistry analysis, we compare the molecular consequences of the p.Y955H mutation to the well-documented p.Y955C mutation. We demonstrate that both mutations affect mtDNA replication and display a dominant negative effect, with the p.Y955H allele resulting in a more severe polymerase dysfunction.
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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.