ArticleAmerican journal of human genetics2023
Trio RNA sequencing in a cohort of medically complex children.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Optimized RNA-seq workflow for routine diagnosis of mitochondrial diseases using aberrant expression analysis and phenotype-driven prioritization.European journal of human genetics : EJHG · 2026Article
- Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.Nature communications · 2026Article
- Novel deep intronic variant in CLCN1 causing autosomal recessive myotonia congenita.Neurogenetics · 2026Article
- Evaluating the Utility of RNAseq in Prenatal Diagnostics: Expression Profiles of Cultured Chorionic Villus and Amniotic Fluid Samples.Prenatal diagnosis · 2026Article
- Translating transcriptomics analysis into diagnostic workflows: clinical variant identification and interpretation in hypothesis-driven and hypothesis-free approaches.EBioMedicine · 2026Article
- RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.Annals of clinical and translational neurology · 2026Article
- Multiomic Investigation of Shared Genetic Pathways in Paediatric Congenital Heart Disease and Neurodevelopmental Disorders.Human mutation · 2026Article
- Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Clinical applications of and molecular insights from RNA sequencing in a rare disease cohort.Genome medicine · 2025Article
- Assessing the diagnostic impact of blood transcriptome profiling in a pediatric cohort previously assessed by genome sequencing.NPJ genomic medicine · 2025Article
- Aberrant gene expression prediction across human tissues.Nature communications · 2025Article
- Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile.European journal of human genetics : EJHG · 2024Article
- Further evidence supporting the role of GTDC1 in glycine metabolism and neurodevelopmental disorders.European journal of human genetics : EJHG · 2024Article
- Explicable prioritization of genetic variants by integration of rule-based and machine learning algorithms for diagnosis of rare Mendelian disorders.Human genomics · 2024Article
- Estimating the proportion of nonsense variants undergoing the newly described phenomenon of manufactured splice rescue.European journal of human genetics : EJHG · 2024Article
- Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.American journal of human genetics · 2023Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome sequencing (GS) is a powerful test for the diagnosis of rare genetic disorders. Although GS can enumerate most non-coding variation, determining which non-coding variants are disease-causing is challenging. RNA sequencing (RNA-seq) has emerged as an important tool to help address this issue, but its diagnostic utility remains understudied, and the added value of a trio design is unknown. We performed GS plus RNA-seq from blood using an automated clinical-grade high-throughput platform on 97 individuals from 39 families where the proband was a child with unexplained medical complexity. RNA-seq was an effective adjunct test when paired with GS. It enabled clarification of putative splice variants in three families, but it did not reveal variants not already identified by GS analysis. Trio RNA-seq decreased the number of candidates requiring manual review when filtering for de novo dominant disease-causing variants, allowing for the exclusion of 16% of gene-expression outliers and 27% of allele-specific-expression outliers. However, clear diagnostic benefit from the trio design was not observed. Blood-based RNA-seq can facilitate genome analysis in children with suspected undiagnosed genetic disease. In contrast to DNA sequencing, the clinical advantages of a trio RNA-seq design may be more limited.
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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.