Diane Fatkin

Damaging RBM20 E-rich domain variants are not rescued by gene replacement

The paper investigates E-rich domain variants of RBM20, showing they reduce protein abundance and cause splicing defects, but are not rescued by RBM20 overexpression.

A Cohort-Based Global Sensitivity Benchmark of MRI-Derived Whole-Heart Electromechanical Models in Healthy Hearts

The paper benchmarks global sensitivity analysis of whole-heart electromechanical models across five healthy subjects, finding haemodynamic parameters dominate cardiac function despite anatomical variation.

Utility of polygenic risk scores in diagnostic genetic testing for dilated cardiomyopathy

This study evaluates polygenic risk scores (PRS) in dilated cardiomyopathy (DCM) patients, finding higher PRS in those without monogenic variants and TTN-related DCM, suggesting polygenic contributions.

Proteo-transcriptomics and morphometrics of teleost cardiac cells define regulatory networks and exercise-induced cardiomyocyte hypertrophy and hyperplasia

The paper develops a workflow for isolating and profiling adult teleost cardiac cells, revealing exercise-induced hypertrophy and hyperplasia and defining proteo-transcriptomic regulatory networks.

Location-Dependent Differences in Cardiac and Skeletal Muscle Dysfunction Associated With Truncating Titin (ttn.2) Variants

This study investigates how truncating variants in the ttn.2 gene affect cardiac and skeletal muscle function in zebrafish, showing location-specific differences in disease severity and phenotypes.

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

Inferring compound heterozygosity from large-scale exome sequencing data

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

Genome-wide association meta-analysis of spontaneous coronary artery dissection reveals common variants and genes related to artery integrity and tissue-mediated coagulation

This study identifies 17 genetic risk loci for spontaneous coronary artery dissection (SCAD), including 12 new ones, and highlights genes related to artery integrity and coagulation.

Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCa1.1, in Sinus Node Function and Arrhythmia Risk

The paper investigates the role of KCa1.1 in sinus node function and arrhythmia risk across species, finding conserved effects of its loss of function.

Cardiac Gq receptors and calcineurin activation are not required for the hypertrophic response to mechanical left ventricular pressure overload

This study shows that Gq receptors and calcineurin are needed for neurohumoral LVH but not for mechanical TAC-induced LVH, which uses CaMKII-HDAC4-MEF2 pathway.

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Over 400 million variants, 97% below 1% frequency, emerge from deep whole-genome sequencing of 53,831 diverse TOPMed participants; TOPMed haplotypes enable imputation down to ~0.01% frequency.

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 210 loci underlying cardiac conduction

This study identifies 210 genetic loci associated with the PR interval through multi-ancestry GWAS, highlighting their role in cardiac conduction and cardiovascular disease.