LQTS-NEXT: to the NEXT level of risk prediction in patients with Long QTS Syndrome
In this project FRRB finances Partner number 5: Istituto Auxologico Italiano I.R.C.C.S., Milano. The Principal Investigator responsible of the project is Dr. Peter J. Schwartz.
|Pathology of interest:||Cardiac arrhythmia|
|Area of research:||Cardiology|
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 noncoding 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.
For more information on the transnational projects funded under the EJP RD Call JTC 2019 visit the following page https://www.ejprarediseases.org/index.php/funded-projects/