Using RNA sequencing to diagnose rare genetic diseases
Official title: Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases
Run by Mario Negri Institute for Pharmacological Research · NCT05996731 · Data updated 2026-11-12
This study is testing if a new RNA sequencing method can help find the genetic causes of rare diseases in people who haven't been diagnosed after other tests.
Quick facts
| Study type | Interventional |
|---|---|
| Sex | All |
| Enrollment | 105 (estimated) |
| Sponsor | Mario Negri Institute for Pharmacological Research Academic / other |
| Locations | 1 site (Ranica, BG) |
| Status | Recruiting |
| Started | February 21, 2024 |
| Main results expected | June 2026 |
| Study ends | June 2026 |
| Registry record updated | March 23, 2026 |
| Trial ID | NCT05996731 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates include adults and children with early-onset undiagnosed rare genetic diseases who have previously tested negative for strong genetic candidates via WES.
✕Probably not a fit
Patients who have already been diagnosed with their genetic condition or those with conditions not related to RNA expression alterations may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This project aims to utilize RNA sequencing technology to uncover genetic alterations in patients with undiagnosed rare diseases, particularly those who have previously undergone whole-exome sequencing (WES) without conclusive results. The study involves setting up and validating transcriptome analysis protocols in both healthy individuals and patients with known RNA expression alterations. It will analyze splicing changes and RNA levels in skin-derived fibroblasts from patients, comparing these profiles to those obtained from blood samples. The ultimate goal is to enhance molecular diagnosis for rare genetic conditions by identifying pathogenic variants that traditional sequencing methods may miss.
Why it matters
Potential benefit: If successful, this approach could lead to more accurate diagnoses for patients with rare genetic diseases, enabling targeted treatments.
How similar studies have gone: While the use of RNA sequencing in diagnosing rare diseases is a growing field, this specific approach focusing on undiagnosed cases represents a novel application.
Who can join: the full rules
Show full inclusion / exclusion criteria
Healthy subjects. Inclusion Criteria: * Male and female adults * Written informed consent Exclusion Criteria: * Inability to understand the potential risk and benefits of the study * Legal incapacity Validation cohort. Inclusion criteria: * Male and female adults * Genetic diseases affecting RNA levels (frameshifts, stop, large deletions, alteration of canonical splicing sites) * Written informed consent Exclusion criteria: * Underage patients * Inability to understand the potential risk and benefits of the study * Legal incapacity Discovery cohort. Inclusion criteria: * Male and female patients (children and adults with onset in infancy or early adulthood) with rare genetic undiagnosed diseases * Patients with no strong candidates based on previous genetic analysis such as WES, but with clinically suspicion of a genetic rare disease * Written informed consent Exclusion criteria: * Inability to understand the potential risk and benefits of the study * Legal incapacity
Where it's running
-
Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"
Ranica, Bg, Italy Recruiting
Study contacts
- Principal investigator: Marina Noris, PhD — Istituto Di Ricerche Farmacologiche Mario Negri
- Study coordinator: Marina Noris, PhD
- Email: marina.noris@marionegri.it
- Phone: +3903545351
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.