ArticleAmerican journal of medical genetics. Part A2020
Limitations of exome sequencing in detecting rare and undiagnosed diseases.
Article in American journal of medical genetics. Part A, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 69 papers.
What it found
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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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
69 citing papers in PubMed, 102 citations in OpenAlex.
- Clinical Utility of Germline Whole-Exome Sequencing Beyond Multigene Panels in Hereditary Cancer.Genes · 2026Review
- Arriving at a diagnosis: Effective strategies used by the Undiagnosed Diseases Network.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Genomic Strategies in Pediatric Care: Addressing Rare Diseases in Children.Children (Basel, Switzerland) · 2026Review
- Article
- Clinicopathologic characterization of a non-expansile, epilepsy-associated neocortical lesion with BRAF K601E mutation.Journal of neuropathology and experimental neurology · 2026Article
- Clinical Utility of Rapid Whole-Genome Sequencing in Hospitalized Adults With Unexplained Neurologic Presentations.Neurology · 2026Article
- The long road to a rare diagnosis: A Malaysian case of childhood-onset progressive myoclonus, ataxia, and retinal dystrophy with biopsy features suggestive of mitochondrial dysfunction.The Journal of international medical research · 2026Article
- Benign Neoplasms in Biallelic Nth-Like DNA Glycosylase 1-Associated Tumor Syndrome: Expanding the Clinical Phenotype.ACG case reports journal · 2026Article
- Bridging the gap: an emerging link between tubulinopathies and ciliopathies.NPJ genomic medicine · 2026Review
- Deep learning detection of retinitis pigmentosa inheritance forms through synthetic data expansion of a rare disease dataset.Scientific reports · 2026Article
- Article
- Enhancing Molecular Diagnostic Accuracy in Genetic Eye Disorders Through a Personalized Re-Evaluation Strategy.Investigative ophthalmology & visual science · 2026Article
- A novel pathogenic mutation in TSPEAR associated with sensorineural hearing loss: a case report and review of the literature.Journal of medical case reports · 2026Review
- From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics.Frontiers in immunology · 2026Review
- Deep Learning Detection of Retinitis Pigmentosa Inheritance Forms through Synthetic Data Expansion of a Rare Disease Dataset.Research square · 2025Article
- Even if a genetic autopsy reveals a pathogenic variant, this should not prevent forensic experts from looking for other causes.Forensic science, medicine, and pathology · 2025Article
- The Undiagnosed Diseases Network (UDN) Solves Ocular Syndromic Diagnostic Dilemmas.American journal of ophthalmology · 2025Article
- Neural Cues and Genomic Clues: NGS Insights into Neurogenic Sarcopenia and Muscle Atrophy.International journal of molecular sciences · 2025Review
- Personalised genomic strategies improve diagnostic yield in inherited retinal dystrophies: a stepwise, patient-centred approach.Eye (London, England) · 2025Article
- Ending diagnostic odyssey by reanalysis of whole exome sequencing data: reclassification of suspected Fanconi anemia cases to dyskeratosis congenita and Diamond-Blackfan anemia.Orphanet journal of rare diseases · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results. Overall, 36/54 (67%) of total diagnoses were based on clinical findings and coding variants found by ES and 3/54 (6%) were based on clinical findings only. The remaining 15/54 (28%) required testing beyond ES. Of these, 7/15 (47%) had NCV, 6/15 (40%) CNV, and 2/15 (13%) had a RE or a DNA methylation disorder. Thus 18/54 (33%) of diagnoses were not solved exclusively by ES. Several methods were needed to detect and/or confirm the functional effects of the variants missed by ES, and in some cases by GS. These results indicate that tests to detect elusive variants should be considered after nondiagnostic preliminary steps. Further studies are needed to determine the cost-effectiveness of tests beyond ES that provide diagnoses and insights to possible treatment.
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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.