N.C. Clinical Genomic Evaluation by NextGen Exome Sequencing (NCGENES)

North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. Participants are patients who were either seen in the UNC Cancer and Adult Genetics Clinic or referred to the study by their physician. They will be approached by their physician or a genetic counselor for recruitment. Once enrolled, a clinical geneticist or genetic counselor will obtain consent and collect blood samples to be analyzed using WES. Results may include information related to a diagnosis and incidental information. Medically actionable incidental findings will be CLIA-certified and returned to participants in a routine genetic counseling session, along with diagnostic findings. Eligible adult participants will be randomized to have the opportunity to choose to get certain types of non-medically actionable incidental findings, as well. Their decisions will be investigated, as will psychosocial and behavioral responses to sequencing and receiving sequencing information. This is a longitudinal, mixed methods study (i.e., multiple assessments pre- and post-return of results, with both quantitative and qualitative methods used to gather data). Because only the quantitative component of the study uses randomization, only measures and procedures associated with that component are included here. The third study release includes data of additional n=189 subjects.]]>
Study participants represent different clinical phenotypes in which delineation of the molecular etiology might be amenable to genome-scale sequencing. The major areas include: Hereditary cancer predisposition Neurological disorders (e.g. neuropathy, myopathy, movement disorders, epilepsy) Intellectual disability and dysmorphology/birth defects Cardiovascular conditions (e.g. Long QT syndrome, cardiomyopathy, thoracic aortic aneurysm and dissection) Retinal disorders Thrombotic disorders Eligible patients should have certain hallmarks - including but not limited to, age of onset, severity, family history, or constellation of phenotypic features - suggestive of a monogenic etiology for their presenting signs or symptoms. Excluded: Those with low suspicion of a hereditable disorder.]]>
2012 - March: First participant visit 2012 - June: First participant's whole exome sequenced 2012 - July: First participant variants analyzed by Molecular Analyst 2012 - September: First participant genetic results independently verified and diagnosed 2013 - January: First Results Discussion visit with participant 2013 - January: First participant randomized in/out of study 2013 - February: First implementation of independent participant ID Check system 2013 - February: First implementation of independent participant ID Check system 2013 - April: First participant report auto-generated 2013 - June: First additional incidental analysis available 2013 - August: First additional incidental analysis requested 2014 - February: First incidental analysis results returned]]>