Connie R. Bezzina

A TMEM175 Mutation Disrupts the Lysosomal-Mitochondrial Axis Causing Short QT Syndrome and Sudden Cardiac Death

This paper identifies a TMEM175 mutation causing short QT syndrome and sudden cardiac death by disrupting lysosomal-mitochondrial interactions and impairing mitochondrial function.

Genetic support for an adverse effect of calcium channel blockers on the human thoracic aorta

This study uses Mendelian randomization to assess the causal role of CACNA1C, a target of calcium channel blockers, on thoracic aortic aneurysm and dissection, finding lower risk with higher aortic expression.

Integrative analysis reveals regulatory effects of tandem repeat expansions in tetralogy of Fallot.

This study identifies rare tandem repeat expansions (TREs) in TOF patients, showing their enrichment in regulatory regions and association with DNA methylation and transcriptional changes.

Transcriptomic and proteomic Mendelian randomization identifies putative therapeutic targets for thoracic aortic disease

This study uses Mendelian randomization to identify 28 putative causal genes for thoracic aortic disease, highlighting potential therapeutic targets.

Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at the SCN5A locus in Brugada syndrome

This study identifies rare and low-frequency non-coding variants at the SCN5A locus associated with Brugada syndrome using whole-genome sequencing and functional assays.

Mapping the genetic landscape of eight common cardiovascular diseases

This study identifies shared genetic factors across eight cardiovascular diseases using large-scale genetic data, revealing clusters and pathways related to vascular biology and systemic risk factors.

Cohort-scale automated patch clamp data improves variant classification and penetrance stratification for SCN5A-Brugada Syndrome

The paper uses automated patch clamp data to reclassify SCN5A variants in Brugada Syndrome, improving variant classification and penetrance stratification.

Genetic modifiers and ascertainment drive variable expressivity of complex disorders

The paper examines how modifier variants affect clinical outcomes in individuals with primary disease variants, showing context-dependent phenotypic associations and synergistic interactions.

Evaluation of polygenic score for hypertrophic cardiomyopathy in the general population and across clinical settings

This study evaluates polygenic scores for hypertrophic cardiomyopathy (HCM) in the general population and clinical settings, showing increased risk with higher scores and potential for clinical application.

The Brugada syndrome associated gene WT1 impacts on SCN5A expression and cardiac conduction

This study shows WT1 regulates SCN5A expression and cardiac conduction in Brugada syndrome through a regulatory element in the RV.

A validated heart-specific model for splice-disrupting variants in childhood heart disease

The paper develops a heart-specific model to predict splice-disrupting variants in childhood heart disease, identifying variants missed by existing tools and showing higher accuracy in cardiac genes.

A rare non-coding enhancer variant in SCN5A contributes to the high prevalence of Brugada syndrome in Thailand

The paper identifies a rare non-coding enhancer variant in SCN5A associated with Brugada syndrome in Thailand, showing it disrupts a transcription factor binding site and reduces sodium current.

Biallelic variants in POPDC2 cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy

Clinical interpretation of KCNH2 variants using a robust PS3/BS3 functional patch clamp assay

The paper establishes a functional patch clamp assay to classify KCNH2 variants in LQTS, using Z-scores to inform ACMG criteria and correlate with clinical scores.

Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: an in-depth genetic exploration of population samples

This study investigates genetic links between schizophrenia and arrhythmic disorders, finding specific genetic correlations and causal effects on Brugada syndrome and heart rate.

Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance

The paper reclassifies a variant in KCNH2 as a low penetrant likely pathogenic variant for LQTS2 based on biophysical effects and clinical variability.

Sequential defects in cardiac lineage commitment and maturation cause hypoplastic left heart syndrome

This study identifies sequential defects in cardiac lineage commitment and maturation in hypoplastic left heart syndrome using multi-omics approaches and iPSC modeling.

Exploring the relationship between schizophrenia and cardiovascular disease: A genetic correlation and multivariable Mendelian randomization study

This study investigates genetic correlations and bidirectional effects between schizophrenia and cardiovascular disease, finding schizophrenia increases heart failure risk and early repolarization risk.

The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

This study identifies genetic overlaps and distinct variant classes in LVNC compared to DCM and HCM, revealing both shared and unique genetic mechanisms.

A Comprehensive Evaluation of the Genetic Architecture of Sudden Cardiac Arrest

This study evaluates the genetic architecture of sudden cardiac arrest through GWAS and Mendelian randomization, finding genetic correlations with CAD, height, BMI, and electrical instability traits.

Deleterious genetic variants in NOTCH1 are a major contributor to the incidence of non-syndromic Tetralogy of Fallot

The paper identifies NOTCH1 variants as a major genetic contributor to non-syndromic Tetralogy of Fallot, with 6% of patients carrying deleterious variants.