Diseases and Abnormalities at or Before Birth

All Conditions

Ear, Nose, and Throat Diseases

Nervous System Diseases

Symptoms and General Pathology

Congenital Abnormalities

Hearing Loss

Deafness

Neurodegenerative Diseases

Neurologic Manifestations

Hearing Disorders

Ear Diseases

Otorhinolaryngologic Diseases

Sensation Disorders

Option to request non-medically actionable incidental information (after receiving education about them)

No option to request non-medically actionable incidental information

Experimental

James P Evans, MD, Ph.D

Gail Henderson, Ph.D

Jonathan S Berg, MD, Ph.D

Christine Rini, Ph.D

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. This sub-project is investigating benefits and harms of providing WES diagnostic and different types of incidental findings to adult patients and parents of pediatric patients who undergo WES because they have symptoms suggesting genetic disease.

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.

NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing

Raw genotype calls from whole exome sequencing are shared with the database of Genotypes and Phenotypes (dbGaP). Other participant demographic variables include: age of onset, birthplace, sex, race, education level, age.

Data is uploaded in batches to the dbGaP website. Currently, the data for 403 participants who have consented for release of their data is available on the dbGaP website.

To access data, users must request authorized access by submitting a Data Use Agreement certified by their institution. This is reviewed by the DbGaP Data Access Committee for approval prior to accessing study data.

All data that is submitted to dbGaP, including individual participant data, is anonymous.

Measured with an adapted version of the multidimensional impact of testing scale (MICRA)

Measure is an adapted version of the multidimensional impact of testing scale MICRA)

Motivations of communications will also be assessed and examined for descriptive analyses.

Participants will answer questions about the extent to which they sought information about whole exome sequencing and results it produces. Questions also ask about sources of that information (e.g., the Internet, doctors) to provide descriptive data about how participants get information.

Also administered 2 wks after return of non-medically actionable incidental results for eligible adult patient participants who request them.

Behaviors include those related to diet, physical activity, smoking, drinking, and substance use.

Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing	NCT01969370	Cancer Cardiovascular ... Neurologic Dysf... Congenital Abno... Hearing Loss	Experimental	-	University of North Carolina, Chapel Hill
NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing	NCT01969370	Cancer Cardiovascular ... Neurologic Dysf... Congenital Abno... Hearing Loss	Experimental	-	University of North Carolina, Chapel Hill
NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing	NCT01969370	Cancer Cardiovascular ... Neurologic Dysf... Congenital Abno... Hearing Loss	Experimental	-	University of North Carolina, Chapel Hill

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