Date of Award
Master of Science (MS)
Craig A. Struble
Francis C. Peterson
Hypoplastic left heart syndrome (HLHS) is a congenital heart defect that leads to neonatal death or compromised quality of life for those affected and their families. This syndrome requires extensive medical intervention for the affected to survive. It is characterized by significant underdevelopment or non-existence of the components of the left heart and the aorta, including the left ventricular cavity and mass. There are many factors ranging from genetics to environmental relationships hypothesized to lead to the development of the syndrome, including recent studies suggesting a link between hearing impairment and congenital heart defects (CHD). Although broadly characterized those factors remain poorly understood. The goal of this project is to systematically utilize bioinformatics tools to determine the relationships of novel mutations found in exome sequencing to a familial congenital heart defect.
A systematic genomic and proteomic approach involving exome sequencing, pathway analysis, and protein modeling was implemented to examine exome sequencing data of a patient with HLHS. Subsequent findings were examined in immediate family members and relatives to investigate inheritance and validate the relationship of novel variants to CHD in the family.
A rare, novel mutation in the LAMA4 gene carried by the proband and other family members may contribute to the development of HLHS in this family.
Available for download on Sunday, May 25, 2014