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

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. 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.

Study Overview

• Status: Recruiting
• Conditions: Genetic Eye Disease

Detailed Description

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. 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.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Bin Guan, Ph.D.; Phone Number: (301) 594-0029; Email: bin.guan@nih.gov
• Study Contact Backup: Name: Delphine M Blain, CGC; Phone Number: (301) 496-1410; Email: delphine.blain@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center,
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

• INCLUSION CRITERIA:

To be eligible, participants must meet the following criteria:

1. 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.
2. Participant or legally authorized representative (LAR) of participant understands and signs the informed consent document.

EXCLUSION CRITERIA:

1. Participants who cannot comply with study procedures are ineligible.
2. Participants who are minors are ineligible if they do not have a parent/LAR 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.
3. Participants who are minors and under joint custody are ineligible if parents disagree about study participation.
4. Prospective participants or their parent/LAR 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Affected participants; Participants with an eye disease.
Unaffected family members; Unaffected family members.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: National Eye Institute (NEI)
• Investigators: Principal Investigator: Bin Guan, Ph.D., National Eye Institute (NEI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2014
• Primary Completion (Estimated): August 5, 2029
• Study Completion (Estimated): August 5, 2029

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: February 28, 2014
• First Posted (Estimated): March 4, 2014

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 19, 2026

More Information

Terms related to this study

• Keywords: Natural History; Genetic Eye Disease; Whole Genome Sequencing
• Additional Relevant MeSH Terms: Eye Diseases
• Other Study ID Numbers: 140064; 14-EI-0064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this time, no IPD will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No