NCGENES: North Carolina Clinical Genomic Evaluation by NextGen 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 University of North Carolina 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 (Clinical Laboratory Improvement Amendments)-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 described here.

• To receive whole exome sequencing in the study, adult or child patients must have a significant chance of having a genetic disorder, as determined by experts on the study team using criteria that depend on the genetic disorder in question. Representative criteria are listed below and will be considered together to determine whether patterns indicate a likely genetic etiology.

Cancer

• Age of diagnosis
• Presence of bilateral (or multiple) cancers
• Diagnosis of a rare type of cancer
• Details of the family history

Cardiovascular Conditions

• Certain clinical findings, such as prolonged QT interval on electrocardiogram.
• Presence of hypertrophic cardiomyopathy or aortic aneurysm
• Age of diagnosis
• Presence of family history

Pediatric neurodevelopmental disorders

• Specific brain structural brain abnormalities
• Presence of certain seizure types
• Dysmorphic features