Julien Barc, partner of a European Joint Programme on Rare Diseases : LQTS-NEXT

  • Le 27 November 2019
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Research projects to accelerate diagnosis and/or explore disease progression and mechanisms of long QT syndrome

Julien Barc, INSERM Associate Researcher, team Cardiovascular genetics, is the French partner of the collaborative project LQTS-NEXT, To the NEXT level of risk prediction in patients with Long QT Syndrome, under the coordination of Connie Bezzina (UMC, Amsterdam, The Netherlands).
This project is laureate of the first call : "European Joint Programme on Rare Diseases Joint Transnational Call 2019".

The aim of the call is to enable scientists in different countries to build an effective collaboration on a interdisciplinary research project based on complementarity expertise for a better patient management: accelerate diagnosis, understand disease progression and molecular mechanisms of the long QT syndrome.

Abstract of LQTS-NEXt project

The discovery of genes underlying the rare inherited cardiac disorders associated with sudden cardiac death (SCD) in the young has led to the routine implementation of genetic testing in the clinical care of patients with these disorders. Yet, with few exceptions, genetic testing has had a relatively modest impact on the ability to predict major clinical events such as SCD. LQTS-NEXT will focus on the Long QT Syndrome (LQTS) as a model to test the hypotheses that (1) additional genetic factors as well as non-genetic parameters (clinical, ECG) conspire with the mutation to modulate disease severity, and (2) the incorporation of such additional genetic and non-genetic parameters in a risk prediction algorithm will provide a refined, personalized, assessment of risk. LQTS-NEXT brings together researchers at the forefront of research and clinical care of LQTS patients with experts in deep learning, to test these hypotheses in the largest cohort of LQTS patients worldwide (>7,000 patients). Crucially, if successful, this project will serve as a template for large-scale genetic and clinical modifier studies in other rare disorders.

Furthermore, LQTS-NEXT will apply cutting edge genomic and bioinformatics approaches to identify the genetic defect underlying LQTS in patients that have remained mutation-negative after extensive gene panel testing of LQTS associated genes. Using state-of-the-art whole genome sequencing and bioinformatic approaches we shall focus on the hypothesis that non- coding region mutations, and intra- and inter-genic rearrangements cause the disorder in a portion of these cases. This work will harness knowledge gained by consortium members and others concerning non-coding regions that are important for gene regulation in the heart (collectively referred to as the cardiac ‘regulome’).

The extensive preliminary work that has been conducted by the LQTS-NEXT partners ensures the feasibility of the project. The standing of the project partners in the field and their network ensures optimal dissemination and implementation of the findings.

Mis à jour le 20 October 2020 - Stéphanie CHATEL.