Stephanie Ware, MD, PhD

Development of a Novel Resequencing Chip to Diagnose Pediatric Cardiomyopathy
Cincinnati Children's Hospital, Cincinnati, OH
Stephanie Ware, MD, PhD – $49,750

Cardiomyopathy is a heart muscle disorder that can be caused by mutations in genes which produce proteins necessary for heart function. While significant progress has been made in identifying the genetic basis of cardiomyopathy in adults, molecular diagnosis in children has proven more challenging. Recent studies indicate that a child's outcome depends on the underlying cause of cardiomyopathy, highlighting the importance of making a precise diagnosis. However, lack of accurate and cost-effective methods for analyzing multiple genes has limited the ability to investigate and precisely diagnose pediatric cardiomyopathy. The goal of this study is to develop and validate a novel resequencing gene chip for the diagnosis of pediatric cardiomyopathy. This new technology allows comprehensive and simultaneous analysis of multiple genes, thereby avoiding many of the historical diagnostic problems. A customized gene chip will be developed to include 30 proteins known to cause cardiomyopathy. It will include the most common genetic causes of cardiomyopathy in adults as well as the genetic causes for metabolic cardiomyopathy, a frequent but relatively uninvestigated cause of cardiomyopathy in children. Since limited genetic studies have been performed in the pediatric population, a second anticipated and important outcome of this study is to determine mutation prevalence in a carefully selected group of pediatric patients. In the first phase of the study, 20 patient DNA samples with known genetic causes of cardiomyopathy will be used to test and validate the gene chip. In the second phase, DNA from 40 patients with a diagnosed mitochondrial disorder and 40 patients with idiopathic cardiomyopathy will be analyzed. This study will give important information about the type and rate of gene mutations in children with cardiomyopathy. Development of novel diagnostic technology will allow for rapid, efficient, and cost-effective detection of genetic causes of cardiomyopathy, which will help management and the development of new treatment strategies.