Using long-read sequencing to diagnose rare genetic diseases

PREcision Diagnostics in Rare genetIC Diseases and Tumors - Long Read Sequencing

This study is testing a new DNA sequencing method to see if it can help people with rare genetic diseases get clearer diagnoses when previous tests didn’t provide answers.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 28 Days and up
• Sex: All
• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna (Academic / other)
• Locations: 1 site (Bologna, Bologna)
• Trial ID: NCT06796751 on ClinicalTrials.gov

What this trial studies

This study utilizes long-read sequencing (LRS) technology to provide molecular diagnoses for patients with rare genetic diseases who have previously received ambiguous or negative results from standard genetic testing. By focusing on the detection of complex structural genomic variants, the study aims to improve the understanding of disease mechanisms and enhance the accuracy of genetic diagnoses. The approach includes analyzing DNA/RNA sequencing data and employing bioinformatics for precise interpretation of genetic information. The goal is to increase diagnostic yield and inform targeted treatment strategies for affected individuals.

Who should consider this trial

Good fit: Ideal candidates include patients or their relatives with uncertain clinical significance from Copy Number Variations (CNVs) or inconclusive Whole Exome Sequencing (WES) results.

Not a fit: Patients with clear pathogenic variants or those not affected by rare genetic diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more accurate diagnoses and better-targeted treatments for patients with rare genetic diseases.

How similar studies have performed: Other studies have shown promise in using long-read sequencing for genetic diagnosis, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

* patients/relatives of patients with Copy Number Variations (CNVs), previously detected by aCGH, with uncertain clinical significance;
* patients/relatives of patients with inconclusive WES and aCGH data (no pathogenic/likely pathogenic variant);
* patients/relatives of patients with a known single hit (a pathogenic or likely pathogenic variant) in an AR gene detected with WES or aCGH;
* patients/relatives of patients with a finding of complex structural variants whose molecular disease mechanism is to be elucidated.

Exclusion Criteria:

* none

Where this trial is running

Bologna, Bologna

• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna, Bologna, Italy (Recruiting)

Study contacts

• Principal investigator: Tommaso Pippucci, Biologist — IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Study coordinator: Tommaso Pippucci, Biologist

Conditions Whole Exome Sequencing; Rare Diseases