Project Details

Early Career

Status: Funded - Open

Identifying candidate genes and molecular mechanisms behind bicuspid aortic valve and LVOTO defects

Emmi Helle, MD, PhD, MSc


BACKGROUND:  Bicuspid aortic valve (BAV) is the most common congenital heart defect affecting 1-2% of the population. BAV is often found in combination with more severe left ventricular outflow tract obstruction (LVOTO) defects such as congenital aortic stenosis, aortic coarctation or hypoplastic left heart syndrome, occuring in about 0.9 of 1000 of all live births. Severe LVOTO defects lead to life-threatening symptoms in the newborn, requiring immediate surgical or catheterization procedures and extensive health care needs during childhood. Even milder, initially asymptomatic LVOTO defects are associated with significant morbidity.

GAP:  LVOTO defects are thought to share similar genetic basis: 10-20% of affected individuals have at least one affected first-degree family member. However, only few genes have been associated with LVOTO defects in humans, explaining only a minority of cases. The aim of the study is to identify new gene variants associated with LVOTO defects.

HYPOTHESIS:  The hypothesis of this study is that variants in multiple genes in molecular pathways engaged in the development of the heart valves are involved in LVOTO defects, the disease thus having an oligogenic origin.

METHODS:  The study population consists of 120 Finnish pediatric LVOTO patients and their family members (total N=248). Candidate genes will be sought by next generation sequencing, and the disease causing potential of the candidate genes will be studied in cell models.

RESULTS: Pending

IMPACT: Identifying genes associated with LVOTO defects will allow genetic testing in families with known predisposition. In addition, it will contribute to identifying individuals at high risk for disease related complications, and provide additional tools for genetic counseling and precision medicine.

Supervising Institution:
Stanford University

Euan Ashley

Project Location:
United States, Finland

Award Amount: