ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
Diagnosing Cornelia de Lange syndrome and related neurodevelopmental disorders using RNA sequencing.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 46 citations in OpenAlex.
- Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics.Genome biology · 2020Trial
- Targeted reflex RNA sequencing for enhanced variant classification on exome and genome sequencing improves patient outcomes.NPJ genomic medicine · 2026Article
- Clinical delineation and genotype-phenotype correlation of 84 pediatric patients with Cornelia de Lange syndrome: insights from a single-center Chinese study.European journal of pediatrics · 2026Article
- RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.Annals of clinical and translational neurology · 2026Article
- Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation.Science advances · 2026Article
- RNA-Seq of Cultured Peripheral Blood Lymphocytes Improves Identification of Cryptic Splicing Defects in Rare Disease Diagnostics.Human mutation · 2026Article
- RNA-guided clarity: The potential for resolving variant uncertainty in clinical exome sequencing.Genetics in medicine open · 2026Article
- Non-Classic Cornelia de Lange Syndrome Due toChildren (Basel, Switzerland) · 2025Review
- Ophthalmological findings in Brazilian Cornelia de Lange syndrome patients with NIPBL variants.BMC ophthalmology · 2025Article
- Cracking rare disorders: a new minimally invasive RNA-seq protocol.NPJ genomic medicine · 2025Article
- Impact of genome build on RNA-seq interpretation and diagnostics.American journal of human genetics · 2024Article
- Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome.Molecular genetics & genomic medicine · 2024Article
- Biallelic variants in GTF3C5, a regulator of RNA polymerase III-mediated transcription, cause a multisystem developmental disorder.Human genetics · 2024Article
- Impact of genome build on RNA-seq interpretation and diagnostics.medRxiv : the preprint server for health sciences · 2024Article
- Transcriptome analyses reveal molecular mechanisms of novel compound heterozygousFrontiers in cellular neuroscience · 2024Article
- Beyond the exome: What's next in diagnostic testing for Mendelian conditions.American journal of human genetics · 2023Review
- Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.American journal of medical genetics. Part A · 2023Article
- Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation.Biomedicines · 2023Review
- Article
- Stepwise use of genomics and transcriptomics technologies increases diagnostic yield in Mendelian disorders.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNeurodevelopmental disorders represent a frequent indication for clinical exome sequencing. Fifty percent of cases, however, remain undiagnosed even upon exome reanalysis. Here we show RNA sequencing (RNA-seq) on human B-lymphoblastoid cell lines (LCL) is highly suitable for neurodevelopmental Mendelian gene testing and demonstrate the utility of this approach in suspected cases of Cornelia de Lange syndrome (CdLS).
methodsGenotype-Tissue Expression project transcriptome data for LCL, blood, and brain were assessed for neurodevelopmental Mendelian gene expression. Detection of abnormal splicing and pathogenic variants in these genes was performed with a novel RNA-seq diagnostic pipeline and using a validation CdLS-LCL cohort (n = 10) and test cohort of patients who carry a clinical diagnosis of CdLS but negative genetic testing (n = 5).
resultsLCLs share isoform diversity of brain tissue for a large subset of neurodevelopmental genes and express 1.8-fold more of these genes compared with blood (LCL, n = 1706; whole blood, n = 917). This enables testing of more than 1000 genetic syndromes. The RNA-seq pipeline had 90% sensitivity for detecting pathogenic events and revealed novel diagnoses such as abnormal splice products in NIPBL and pathogenic coding variants in BRD4 and ANKRD11.
conclusionThe LCL transcriptome enables robust frontline and/or reflexive diagnostic testing for neurodevelopmental disorders.
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