Using RNA sequencing to diagnose rare genetic diseases
Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases
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
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 105 (estimated) |
| Sex | All |
| Sponsor | Mario Negri Institute for Pharmacological Research Academic / other |
| Locations | 1 site (Ranica, BG) |
| Trial ID | NCT05996731 on ClinicalTrials.gov |
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.
Who should consider this trial
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.
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.
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 performed: 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.
Eligibility criteria
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 this trial is running
Ranica, BG
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.