ArticleScience translational medicine2012
Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers, 2 of them syntheses 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
238 citing papers in PubMed, 2 syntheses or guidelines pooled it, 472 citations in OpenAlex.
- Systematic review of Leber's hereditary optic neuropathy - Clinical diagnosis, genetics overview and current concepts of treatment.Indian journal of ophthalmology · 2026Pooled it
- Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase.Physiological research · 2024Pooled it
- Genetic Screening of Patients With Inherited Fanconi Syndrome.Kidney international reports · 2026Article
- Historical Perspectives, Classification and Diagnostic Approaches of Inborn Errors of Metabolism: A Systematic Review and Meta-Analysis.Metabolites · 2026Review
- Systemic delivery of AAV-GFM1 corrects COXPD1 molecular alterations in Gfm1EMBO molecular medicine · 2026Article
- Oocyte-specific acylglycerol kinase loss leads to infertility in mice via mitochondrial dysfunction.Communications biology · 2026Article
- Systematic performance evaluation and application validation of an end-to-end NGS workstation.Scientific reports · 2026Article
- Mitochondrial tRNAHuman mutation · 2026Article
- A systems genetics approach to uncover mitochondrial drivers of heart failure reveals mitochondria-nuclear cross talk in genetically diverse mouse strains.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial disease management through phytochemical interventions.Molecular and cellular biochemistry · 2025Review
- Untargeted proteomics enables ultra-rapid variant prioritisation in mitochondrial and other rare diseases.Genome medicine · 2025Article
- CHCHD4 Oxidoreductase Activity: A Comprehensive Analysis of the Molecular, Functional, and Structural Properties of Its Redox-Regulated Substrates.Molecules (Basel, Switzerland) · 2025Review
- AARS2-catalyzed lactylation induces follicle development and premature ovarian insufficiency.Cell death discovery · 2025Article
- Sengers syndrome caused by biallelic TIMM29 variants and RNAi silencing in Drosophila orthologue recapitulates the human phenotype.Human genomics · 2025Review
- Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.Cellular & molecular biology letters · 2025Article
- Identification of genetic mechanisms of non-isolated auditory neuropathy with various phenotypes in Chinese families.Orphanet journal of rare diseases · 2025Article
- 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
- IARS2 mutations lead to Leigh syndrome with a combined oxidative phosphorylation deficiency.Orphanet journal of rare diseases · 2024Article
- Review
- More than Just Bread and Wine: Using Yeast to Understand Inherited Cytochrome Oxidase Deficiencies in Humans.International journal of molecular sciences · 2024Review
178 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
17 authors at 10 institutions in 3 countries.
Funding
Abstract
Advances in next-generation sequencing (NGS) promise to facilitate diagnosis of inherited disorders. Although in research settings NGS has pinpointed causal alleles using segregation in large families, the key challenge for clinical diagnosis is application to single individuals. To explore its diagnostic use, we performed targeted NGS in 42 unrelated infants with clinical and biochemical evidence of mitochondrial oxidative phosphorylation disease. These devastating mitochondrial disorders are characterized by phenotypic and genetic heterogeneity, with more than 100 causal genes identified to date. We performed "MitoExome" sequencing of the mitochondrial DNA (mtDNA) and exons of ~1000 nuclear genes encoding mitochondrial proteins and prioritized rare mutations predicted to disrupt function. Because patients and healthy control individuals harbored a comparable number of such heterozygous alleles, we could not prioritize dominant-acting genes. However, patients showed a fivefold enrichment of genes with two such mutations that could underlie recessive disease. In total, 23 of 42 (55%) patients harbored such recessive genes or pathogenic mtDNA variants. Firm diagnoses were enabled in 10 patients (24%) who had mutations in genes previously linked to disease. Thirteen patients (31%) had mutations in nuclear genes not previously linked to disease. The pathogenicity of two such genes, NDUFB3 and AGK, was supported by complementation studies and evidence from multiple patients, respectively. The results underscore the potential and challenges of deploying NGS in clinical settings.
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.