Current Focus: Splice Variants First

Despite our podcast name, we’re going beyond DNA in this episode and into the next frontier of genetic diagnostics: RNA sequencing and multi-omics.

While DNA sequencing often reveals variants of uncertain significance (VUS), RNA sequencing provides functional evidence that can resolve uncertainty, uncover splicing abnormalities, and ultimately shorten the diagnostic odyssey for patients with rare diseases.

Joining for this in-person podcast episode is Dr. Christine Eng, Chief Medical Officer and Chief Quality Officer at Baylor Genetics, and Vice Chair for Diagnostic Laboratory Affairs at Baylor College of Medicine. Dr. Eng has been a pioneer in implementing genomics into clinical practice, and her work is shining a light on how RNAseq and multi-omic approaches are transforming the way we diagnose and care for patients.

• RNAseq 101: What RNA sequencing is and how it complements DNA sequencing.
• Splicing Abnormalities: What RNAseq can reveal that DNA sequencing may miss.
• Clinical Impact: Real-world examples, including a case where RNAseq reclassified a VUS and changed patient care.
• Diagnostic Yield: How often Baylor Genetics sees clinical benefit from RNAseq.
• Workflow Questions: Should RNAseq be a reflex after WES/WGS fails to identify a pathogenic variant?
• Technical Realities: Key challenges including tissue type, RNA quality, and turnaround time.
• When Results Are Inconclusive: How to handle unexpected or unclear RNA findings.
• Beyond RNAseq: How multi-omics (including transcriptomics and metabolomics) are beginning to integrate into clinical practice.
• Implementation Barriers: Challenges to scaling multi-omic testing in routine labs.
• Future of Clinical Genomics: Dr. Eng’s predictions for RNAseq and multi-omics adoption over the next decade.
  
  

• Learn more about Baylor Genetics here
• Baylor Genetics Webinar: From Symptoms to Sequencing: Diagnostic Insights from 3 Pediatric Genome Sequencing Cases
• AAP’s Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report
• Baylor Genetics Applauds New Guidance from American Academy of Pediatrics for Genome and Exome Sequencing to be used as First-Tier Tests for Children with Certain Developmental Delays
• Dr. Christine Eng’s Presentation “How Whole Genome Sequencing Can Lead to Early Diagnosis and Intervention”
• Zhao S, Macakova K, Sinson JC, Dai H, Rosenfeld J, Zapata GE, Li S, Ward PA, Wang C, Qu C, Maywald B; Undiagnosed Diseases Network; Lee B, Eng C, Liu P. Clinical validation of RNA sequencing for Mendelian disorder diagnostics. Am J Hum Genet. 2025 Apr 3;112(4):779-792. doi: 10.1016/j.ajhg.2025.02.006. Epub 2025 Mar 4. PMID: 40043707; PMCID: PMC12081282.
• Undiagnosed Disease Network

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