Congenital heart disease (CHD) is one of the most common major malformations occurring in 4-8/1000 live births. The etiology of CHD is thought to be multifactorial; both genetic and environmental factors have been implicated. However, few precise genetic or environmental causes have been defined. Data suggests that there is a genetic basis for the development of left-sided obstructive cardiac lesions and that these defects may be familial more frequently than recognized. Left sided obstructive lesions include hypoplastic left heart syndrome, valvular aortic stenosis, coarctation of the aorta, bicuspid aortic valve and mitral valve abnormalities; together they comprise 13% of all types of CHD. This program is investigating the genetic etiology of left-sided cardiac defects by performing clinical and laboratory based studies. Families with at least one member with a left-sided obstructive lesion are evaluated to determine whether the disease is familial. To this end, a detailed family history for congenital heart disease or extracardiac congenital malformations is obtained. Further, the first-degree relatives (parents and siblings) of patients with a left sided obstructive lesion are being examined by echocardiography for the presence of subclinical cardiac defects, such as a clinically silent bicuspid aortic valve. Samples of whole blood from the proband and from their parents, siblings and other relatives (where applicable) are being collected simultaneously thereby developing a clinical database and DNA bank for molecular studies. Molecular investigations have been initiated to screen two candidate genes for mutations in affected subjects.
Showing the most recent 10 out of 455 publications
