Mutations in genes related to myocyte contraction and ventricular septum development in non-syndromic tetralogy of Fallot.

Objective: Eighty percent of patients with a diagnosis of tetralogy of Fallot (TOF) do not have a known genetic etiology or syndrome. We sought to identify key molecular pathways and biological processes that are enriched in non-syndromic TOF, the most common form of cyanotic congenital heart disease, rather than single driver genes to elucidate the pathogenesis of this disease.

Methods: We undertook exome sequencing of 362 probands with non-syndromic TOF and their parents within the Pediatric Cardiac Genomics Consortium (PCGC).

Delta-like ligand-4 regulates Notch-mediated maturation of second heart field progenitor-derived pharyngeal arterial endothelial cells.

Mesodermal progenitors in the second heart field (SHF) express Delta-like-ligand 4 (Dll4) that regulates Notch-mediated proliferation. As cells of SHF lineage mature to assume endocardial and myocardial cell fates, we have shown that Dll4 expression is lost, and the subsequent expression of another Notch ligand Jagged1 regulates Notch-mediated maturation events in the developing heart. A subset of SHF progenitors also matures to form the pharyngeal arch artery (PAA) endothelium.

Educational, psychosocial, and clinical impact of SARS-CoV-2 (COVID-19) pandemic on medical students in the United States.

Background: The coronavirus disease 2019 (COVID-19) pandemic altered education, exams, and residency applications for United States medical students.

Aim: To determine the specific impact of the pandemic on US medical students and its correlation to their anxiety levels.

Methods: An 81-question survey was distributed email, Facebook and social media groups using REDCap.

Association of Alcohol Use Diagnostic Codes in Pregnancy and Offspring Conotruncal and Endocardial Cushion Heart Defects.

Background The pathogenesis of congenital heart disease (CHD) remains largely unknown, with only a small percentage explained solely by genetic causes. Modifiable environmental risk factors, such as alcohol, are suggested to play an important role in CHD pathogenesis. We sought to evaluate the association between prenatal alcohol exposure and CHD to gain insight into which components of cardiac development may be most vulnerable to the teratogenic effects of alcohol.

Concomitant genetic defects potentiate the adverse impact of prenatal alcohol exposure on cardiac outflow tract maturation.

Background: Prenatal alcohol exposure (PAE) is associated with an increased incidence of congenital heart defects (CHD), in particular outflow tract (OFT) defects. However, the variability in the incidence of CHD following PAE has not been fully explored. We hypothesize that a concomitant, relevant genetic defect would potentiate the adverse effect of PAE and partially explain the variability of PAE-induced CHD incidence.

Murine Model of Cardiac Defects Observed in Adams-Oliver Syndrome Driven by Haploinsufficiency.

Heterozygous loss-of-function mutation in Delta-like ligand-4 () is an important cause of Adams-Oliver syndrome (AOS). Cardiac defects, in particular outflow tract (OFT) alignment defects, are observed in about one-fourth of patients with this syndrome. The mechanism underlying this genotype-phenotype correlation has not yet been established.