RNA to the RESCUE: Evaluation to Assess the Clinical Utility of RNA Sequencing in Establishing a Genetic Diagnosis or Adjudicating a Previously Established Genetic Diagnosis.

RNAseq for the Evaluation of Splicing and Cryptic or Unrecognized Effects

The goal of this observational study is to see if ribonucleic acid (RNA) sequencing can improve the diagnostic yield and accuracy of genetic testing compared to gene sequencing alone. Participants will be asked to share their medical history and prior genetic testing results, and to donate a blood sample for testing.

Study Overview

• Status: Recruiting
• Conditions: Genetic Disorders; Genetic Conditions
• Intervention / Treatment: Device: RNA sequencing

Detailed Description

Participant will come on site for a one-time blood draw. Study personnel will review prior medical history, family history, and prior genetic testing results gathered from the participant's medical record, along with analysis of RNA sequencing results derived from participant's blood sample. Results will be shared with participants through their clinical geneticist.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Janice Light; Phone Number: 415-502-6184; Email: janice.light@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94159
      • Recruiting
      • University of California, San Francisco
      • Contact: Janice Light; Phone Number: 415-502-6184; Email: janice.light@ucsf.edu
      • Principal Investigator: Kanika Bhardwaj
      • Principal Investigator: Reva Frankel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients seen by the division of Medical Genetics

Description

Inclusion Criteria:

• individuals who have previously undergone gene panel testing, WES or WGS with no diagnostic findings but with high suspicion for a genetic etiology
• individuals who have undergone genetic testing and who are found to have a truncating variant classified as pathogenic in a disease-causing gene but lack many/all symptoms typically associated with the disorder.

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No genetic diagnosis; Individuals who have previously undergone gene panel testing, WES or WGS with no diagnostic findings but with high suspicion for a genetic etiology	Device: RNA sequencing; Total RNA will be isolated from blood samples, processed, and analyzed to compare the RNA-Seq profile of each participant.
No symptomatology; Individuals who have undergone genetic testing and who are found to have a truncating variant classified as pathogenic in a disease-causing gene but lack many/all symptoms typically associated with the disorder	Device: RNA sequencing; Total RNA will be isolated from blood samples, processed, and analyzed to compare the RNA-Seq profile of each participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RNA analysis supports that the gene variant impacts gene expression	RNA-Seq analysis shows that the gene variant of interest impacts the gene expression with either a decreased expression, increased expression, alternative splice product, or other.	From analysis of RNA-Seq data to finalized summary of research results (up to 1 year)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Results add value to the diagnostic process	Clinical geneticist will complete a survey to indicate if they found that the research results added value to the diagnostic process.	From clinical geneticist receiving research results to share with participant to the completion of survey (up to 3 months)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Kanika Bhardwaj, University of California, San Francisco; Principal Investigator: Reva Frankel, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: August 21, 2026
• First Submitted That Met QC Criteria: August 21, 2026
• First Posted (Actual): August 26, 2026

Study Record Updates

• Last Update Posted (Actual): August 26, 2026
• Last Update Submitted That Met QC Criteria: August 21, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: RNA sequencing; RNA to the RESCUE
• Additional Relevant MeSH Terms: Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Investigative Techniques; Genetic Techniques; Sequence Analysis; Sequence Analysis, RNA
• Other Study ID Numbers: 23-39430

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes