GenLab: Unveiling the Genetic Landscape of Brugada Syndrome: Novel Biomarker Discovery for Precise Diagnosis (GenLaB)

Unveiling the Genetic Landscape of Brugada Syndrome: Novel Biomarker Discovery for Precise Diagnosis

This research makes several significant contributions to the field of BrS. It employs advanced genetic sequencing techniques to develop a genetic signature to improve the accuracy and efficiency of BrS diagnosis. The identification of specific biomolecular profiles and genetic signatures enhances our understanding of the syndrome's molecular mechanisms, facilitating targeted therapies and refined risk stratification. These advancements optimize patient care by enabling personalized treatment plans and risk assessment. Overall, this research adds value by advancing diagnostic methods, providing molecular insights, optimizing patient care, and positively impacting public health outcomes in BrS.

Study Overview

• Status: Recruiting
• Conditions: Brugada Syndrome (BrS)

Detailed Description

Our work on BrS is dedicated to decipher the pathogenic mechanism and to ameliorate diagnostic approaches by developing a non-invasive test. Employing a multi-omic strategy, we've identified potential biomarkers across proteins, metabolites, and lipids, leading to a filed patent for a promising biomolecular signature. Additionally, we've discovered associated gene mutations. This grant proposal aims to enhance our preliminary findings by studying a larger BrS cohort, supported by a meticulously curated patient registry. By integrating advanced whole-exome sequencing (WES) and machine learning , we aim to identify a genetic signature for BrS diagnosis and uncover altered pathways integral to BrS etiology. This could refine risk stratification strategies, contributing to improved diagnostic accuracy and deeper understanding BrS molecular mechanisms.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Giuseppe Ciconte MD, PhD; Phone Number: +390252774260; Email: Giuseppe.Ciconte@grupposandonato.it

Study Locations

• Italy
  • Milan
    • San Donato Milanese, Milan, Italy, 20097
      • Recruiting
      • IRCCS Policlinico San Donato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

A total of 350 patients affected by BrS coming from the same geographical area and age-sex balanced, when it's possible. The total sample includes at least 300 individuals from Sardinia, to whom pre-existing data of 100 patients will be added, already subject to the Whole Exome Sequencing (WES) at Policlinico San Donato.

Description

Inclusion Criteria:

• Age > 18 years
• Patients affected by Brugada Syndrome
• Patients who signs the Informed Consent

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
BrS Affected; The Study population will be composed by patients affected by the Brugada Syndrome, including both the ones already under teatment and subjects with new diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multigenic Risk Score (MRS)	Our objective is to utilize the extensive Whole-Exome Sequencing (WES) data from our cohort to discover shared genetic mechanisms underlying BrS. We will conduct rigorous quality control and genome-wide association analyses to identify both common and rare mutations related to BrS. We aim to develop a Multigenic Risk Score (MRS) based on the cumulative findings, considering the effects of associated variants on protein and gene expression levels, and chromatin structure. The MRS seeks to refine the BrS biomarker panel and develop a robust diagnostic tool for BrS by leveraging genetics, machine learning, and translational research.	from October 2025 to June 2026

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato
• Collaborators: Azienda Ospedaliero Universitaria di Sassari; National Research Council of Italy

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Genetic Diseases, Inborn; Disease; Arrhythmias, Cardiac; Brugada Syndrome; Syndrome
• Other Study ID Numbers: PNRR-POC-2023-12378388

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No