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.

University of California, San Francisco100 enrolled

Overview

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.

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

100

Conditions

Genetic Conditions Genetic Disorders

Interventions

RNA sequencingDEVICE

Total RNA will be isolated from blood samples, processed, and analyzed to compare the RNA-Seq profile of each participant.

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: From analysis of RNA-Seq data to finalized summary of research results (up to 1 year)