Genetic Eye Disease

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....

Background: Research has identified some of the genes involved in inherited eye diseases. But for many of these diseases, the genes are not yet known. Researchers want to try to find these genes. They also hope to learn more about how symptoms differ in people with similar gene changes. Objective: To learn more about genes involved in eye diseases. Eligibility: People who have a known or suspected inherited eye disease, and their relatives. Design: * All participants will have a medical history, physical exam, and eye exam. They will have blood taken. * Participants with an eye disease may have eye cell samples taken using a swab or biopsy procedure. * Participants may have a skin biopsy. A 3mm piece of skin will be removed. * Participants may provide samples of tears, urine, saliva, stool, hair, or inner cheek cells. * Participants may have a retina test. They may also have a test that uses light to measure retina thickness. * Participants may have an eye movement test. Electrodes will be placed on the skin next to both eyes. * Participants may have a fluorescein angiography. A dye will be given through an intravenous line in the arm. A camera will take pictures of the dye as it flows through the eyes blood vessels. * Participants may have microperimetry. They will sit at a computer screen and press a button when they see a light. * Participants may have an eye movement test. They will wear contact lenses or goggles and watch a series of spots on a computer screen. * Participants may complete a color vision test. * Participants will provide a specimen for genetic testing. * Participants may have a MRI. * Participants may complete questionnaires.