Gerald F. Cox, MD, PhD

Analysis of Sarcomere Gene Mutations in Pediatric Hypertrophic Cardiomyopathy
Children's Hospital, Boston, MA
Gerald F. Cox, MD, PhD – $60,000

The purpose of this study is to determine whether sarcomere gene mutations are a common cause of hypertrophic cardiomyopathy (HCM) in children, and if so, how they influence the disease. In adults, HCM can be caused by mutations in 10 different genes encoding sarcomeric proteins of the contractile apparatus, which allows the heart to pump blood. In children, however, the causes of HCM are poorly understood and more varied. This study will recruit 50 subjects with HCM from the Pediatric Cardiomyopathy Registry, with approximately equal numbers diagnosed in infancy or later (2 to 18 years) and equal numbers with or without a family history of HCM. The coding regions of 8 sarcomeric genes (MHC, MBP, TNNT2, TNNI3, TTN1, alpha-actin, MLC2, and MLC3) will be fully sequenced in all patients to identify possible mutations. The study will attempt to answer the following questions: is the earlier age of onset of HCM in children compared to adults due to the presence of two mutations, different frequencies of involved genes, or other mutations in the same genes? Do the mutations correlate with clinical features and echocardiographic findings? Does HCM caused by sarcomeric gene mutations differ from HCM related to other causes? These results may help decide which children with HCM should undergo testing for sarcomere gene mutations and how the testing should be carried out.