ArticleNeurology2013
Targeted exome sequencing of suspected mitochondrial disorders.
Article in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase.Physiological research · 2024Pooled it
- Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.BMJ (Clinical research ed.) · 2021Trial
- Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.EMBO molecular medicine · 2026Article
- Hypoxia-driven microRNA-27b underlies pathologic cardiac endoreplication in heart disease.Signal transduction and targeted therapy · 2026Article
- Studies on intellectual disability identify variants in established genes as well as confirm candidature of new genes.Scientific reports · 2026Article
- Untargeted Metabolomics for Diagnosis, Monitoring, and Understanding the Pathophysiology of Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- ATP5F1A deficiency causes developmental delay and motor dysfunction in humans and zebrafish.Journal of translational medicine · 2025Article
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- Dominant negative ATP5F1A variants disrupt oxidative phosphorylation causing neurological disorders.EMBO molecular medicine · 2025Article
- Hyperkinetic Movement Disorder inNeurology international · 2025Article
- Expanding the Allelic and Clinical Heterogeneity of Movement Disorders Linked to Defects of Mitochondrial Adenosine Triphosphate Synthase.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Setting the Stage for Treatment of Aminoacyl-tRNA Synthetase (ARS)1-Deficiencies: Phenotypic Characterization and a Review of Treatment Effects.Journal of inherited metabolic disease · 2025Review
- A Review over Mitochondrial Diseases Due to mtDNA Mutations: Recent Advances and Remedial Aspects.Infectious disorders drug targets · 2025Review
- Genetic landscape of primary mitochondrial diseases in children and adults using molecular genetics and genomic investigations of mitochondrial and nuclear genome.Orphanet journal of rare diseases · 2024Article
- POLG2-Linked Mitochondrial Disease: Functional Insights from New Mutation Carriers and Review of the Literature.Cerebellum (London, England) · 2024Review
- A Homozygous Missense Variant inMolecular syndromology · 2024Article
- BEDwARS: a robust Bayesian approach to bulk gene expression deconvolution with noisy reference signatures.Genome biology · 2023Article
- Growth arrest and DNA damage-inducible alpha regulates muscle repair and fat infiltration through ATP synthase F1 subunit alpha.Journal of cachexia, sarcopenia and muscle · 2023Article
- Precision mitochondrial medicine.Cambridge prisms. Precision medicine · 2023Review
- Genomic Strategies in Mitochondrial Diagnostics.Methods in molecular biology (Clifton, N.J.) · 2023Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveTo evaluate the utility of targeted exome sequencing for the molecular diagnosis of mitochondrial disorders, which exhibit marked phenotypic and genetic heterogeneity.
methodsWe considered a diverse set of 102 patients with suspected mitochondrial disorders based on clinical, biochemical, and/or molecular findings, and whose disease ranged from mild to severe, with varying age at onset. We sequenced the mitochondrial genome (mtDNA) and the exons of 1,598 nuclear-encoded genes implicated in mitochondrial biology, mitochondrial disease, or monogenic disorders with phenotypic overlap. We prioritized variants likely to underlie disease and established molecular diagnoses in accordance with current clinical genetic guidelines.
resultsTargeted exome sequencing yielded molecular diagnoses in established disease loci in 22% of cases, including 17 of 18 (94%) with prior molecular diagnoses and 5 of 84 (6%) without. The 5 new diagnoses implicated 2 genes associated with canonical mitochondrial disorders (NDUFV1, POLG2), and 3 genes known to underlie other neurologic disorders (DPYD, KARS, WFS1), underscoring the phenotypic and biochemical overlap with other inborn errors. We prioritized variants in an additional 26 patients, including recessive, X-linked, and mtDNA variants that were enriched 2-fold over background and await further support of pathogenicity. In one case, we modeled patient mutations in yeast to provide evidence that recessive mutations in ATP5A1 can underlie combined respiratory chain deficiency.
conclusionThe results demonstrate that targeted exome sequencing is an effective alternative to the sequential testing of mtDNA and individual nuclear genes as part of the investigation of mitochondrial disease. Our study underscores the ongoing challenge of variant interpretation in the clinical setting.
Indexed as
Identifiers
What OpenQuestion holds
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.