ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Pitfalls of clinical exome and gene panel testing: alternative transcripts.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
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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.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- A Novel Cause of CIDP: Homozygous Hotspot Mutation, c.793 C > T in CASP8 Gene.Journal of clinical immunology · 2025Review
- Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families.Nature communications · 2023Article
- The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.Scientific reports · 2022Article
- What Has the Undiagnosed Diseases Network Taught Us About the Clinical Applications of Genomic Testing?Annual review of medicine · 2022Review
- Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies.Current neuropharmacology · 2021Review
- A fully-automated event-based variant prioritizing solution to the CAGI5 intellectual disability gene panel challenge.Human mutation · 2019Article
- Increased diagnostic yield by reanalysis of data from a hearing loss gene panel.BMC medical genomics · 2019Article
- Review
- Metabolic Evaluation of Epilepsy: A Diagnostic Algorithm With Focus on Treatable Conditions.Frontiers in neurology · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeClinical exome and gene panel testing can provide molecular diagnoses for patients with rare Mendelian disorders, but for many patients these tests are nonexplanatory. We investigated whether interrogation of alternative transcripts in known disease genes could provide answers for additional patients.
methodsWe integrated alternative transcripts for known neonatal epilepsy genes with RNA-Seq data to identify brain-expressed coding regions that are not evaluated by popular neonatal epilepsy clinical gene panel and exome tests.
resultsWe found brain-expressed alternative coding regions in 89 (30%) of 292 neonatal epilepsy genes. The 147 regions encompass 15,713 bases that are noncoding in the primary transcripts analyzed by the clinical tests. Alternative coding regions from at least 5 genes carry reported pathogenic variants. Three candidate variants in these regions were identified in public exome data from 337 epilepsy patients. Incorporating alternative transcripts into the analysis of neonatal epilepsy genes in 44 patient genomes identified the pathogenic variant for the epilepsy case and 2 variants of uncertain significance (VUS) among the 43 control cases.
conclusionAssessment of alternative transcripts in exon-based clinical genetic tests, including gene panel, exome, and genome sequencing, may provide diagnoses for patients for whom standard testing is unrevealing, without introducing many VUS.
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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.