Precision Diagnosis and Therapy for Rare Diseases by Interpreting Non-coding Genomes

Launched by IRCCS AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA · Jan 9, 2025

Keywords

ClinConnect Summary

The PARADIGM study is looking into how genetic information from patients can help diagnose and treat rare diseases, specifically focusing on eye diseases and neuromuscular diseases. These conditions are complex because they can be caused by different genes, and sometimes the important genetic changes are not found in the typical areas scientists usually look at. The goal of this trial is to better understand these hidden genetic factors and explore new treatment options that have been developed by the research team.

To participate in this study, you or your family member should have a clinical diagnosis of either an eye disease or a neuromuscular disease. If previous genetic tests didn’t provide clear answers, or if only one genetic change was found in a specific type of gene, you may also be eligible. Participants will need to sign a consent form to take part in the study. It's important to note that families where both parents are unaffected will not be included unless a sufficient number of affected family members are involved. By joining this study, participants can contribute to important research that may lead to better understanding and treatment options for these challenging conditions.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • patients/relatives of patients with clinical diagnosis of NMD/ED;
• • patients/relatives of patients with inconclusive ES and aCGH data (no pathogenic/likely pathogenic variant) or finding of only a single hit (a pathogenic or likely pathogenic variant) in an autosomal recessive gene by ES (or aCGH) or no pathogenic or likely pathogenic variant but detection of a large region of genomic homozygosity surrounding a candidate gene;
• • patients/relatives of patients with a finding of cryptic VUS (splicing/regulatory/noncoding CNVs) in ED/NMD genes or pathogenic cryptic variants in a selected number of representative cases.
• • Signed informed consent to participate in the study.
• Exclusion Criteria:
• • - Trios or nuclear families where both unaffected parents do not consent to participate will be excluded (similarly, a minimum number of 3 affected family members will be needed in multigenerational pedigrees).