Whole Exome and Whole Genome Sequencing for Genotyping of Inherited and Congenital Eye Conditions

NCT02077894 | Recruiting

• 2 other identifiers: 14006414-EI-0064
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: The objective of this study is to identify genetic causes of inherited eye conditions through whole exome or whole genome sequencing (referred to as exome sequencing and genome sequencing in the remainder of the document). This includes identifying mutations in known genes or novel genes for recognized conditions, as well as identifying mutations in novel genes for previously uncharacterized genetic conditions involving the eye. Study Population: We plan to recruit 2,000 participants, to include both participants with an eye condition under study and unaffected family members. Ideally unaffected family members will be parents of an affected participant. Design: Participants will be self-referred or referred by an outside clinician. They will preferably be evaluated at the National Institutes of Health (NIH), but the option to participate offsite will be offered. Participants evaluated onsite will be recruited through other pre-existing NIH protocols, such as the National Eye Institute (NEI) Screening protocol (08-EI-0102), the NEI Ocular Natural History protocol (16-EI-0134), the Genetics of Inherited Eye Disease protocol (15-EI-0128), and the Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC) protocol (13-EI-0049). Offsite participants will be screened via phone or secure videoconference, and records will be requested for evaluation of affected participants. Both affected and unaffected eligible participants will undergo genetic counseling and will provide a blood sample and/or saliva sample for exome or genome sequencing. Biological relationships will be confirmed prior to exome or genome sequencing. Sequence data will be analyzed for primary variants and secondary findings, unless participants choose to opt-out of secondary analysis and reporting. All sequence variants deemed clinically relevant will be validated in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory and the results will be returned to the participant in-person, secure videoconference, or by telephone. Outcome Measures: This is an etiologic study that will generate molecular information about previously-recognized conditions for which participants did not have a molecular diagnosis, as well as molecular information for previously uncharacterized conditions involving the eye.

Conditions

Genetic Eye Disease

Keywords

Whole Genome Sequencing; Genetic Eye Disease; Natural History

Outcome Measures

Primary Outcomes (1)

• This is an etiologic study that will generate new genes or variants for inherited eye diseases.

  This is an etiologic study that will generate molecular information about previously-recognized conditions for which participants did not have a molecular diagnosis, as well as molecular information for previously uncharacterized eye conditions.

  Until the affected participant has received confirmed Primary Results (PRs). Unaffected family members may or may not receive any results, but their participation will be ongoing until their affected family member receives PRs.

Study Arms (2)

Affected participants

Participants with an eye disease.

Unaffected family members

Unaffected family members.

Eligibility Criteria

• Age: 1 Day - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study seeks to recruit patients with a diagnosis of inherited or congenital eye condition whose phenotype was confirmed either at the National Eye Institute (NEI) or through an outside clinician such as an ophthalmologist or geneticist. Select unaffected family members (in many cases, parents) will also be recruited in order to facilitate data analysis.

You may qualify if:

• To be eligible, participants must meet the following criteria:
• Participant is affected with an eye condition under study or is a family member of an affected individual who will be informative for ES/GS analysis and interpretation.
• Participant or legal guardian of participant understands and signs the informed consent document.

You may not qualify if:

• Participants who cannot comply with study procedures are ineligible.
• Participants who are minors are ineligible if they do not have a parent/legal guardian who can consent and make decisions on their behalf. Participants who are or become decisionally impaired are ineligible if they do not have, or are unable to obtain, a legally authorized representative who can consent and make decisions on their behalf.
• Participants who are minors and under joint custody are ineligible if parents disagree about study participation.
• Prospective participants or their parent/legal guardians or legally authorized representatives who, based on the judgment of the team, appear to have impaired ability to understand and appropriately use complex medical and genetic information, or to cope with potentially life altering medical information, will be ineligible.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center,

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Bin Guan, Ph.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Delphine M Blain, CGC

CONTACT

(301) 496-1410; delphine.blain@nih.gov

Bin Guan, Ph.D.

CONTACT

(301) 594-0029; bin.guan@nih.gov

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2014
• First Posted: March 4, 2014
• Study Start: August 5, 2014
• Primary Completion (Estimated): August 5, 2029
• Study Completion (Estimated): August 5, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-03-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)