Clinical and Molecular Studies in Families With Inherited Eye Disease
Clinical and Molecular Studies in Families With Inherited Eye Disease
Background:

 Genes are the basic units of heredity. When genes are changed, certain cells don t work like
 they should. Researchers want to try to better understand the genetic conditions that are
 linked with inherited eye diseases.

 Objective:

 To try to identify the genes linked to the development of inherited eye diseases.

 Eligibility:

 People ages 4 and older who have or have a family member with an inherited eye disease

 Design:

 Participants will be screened with medical history and medical records.

 Participants will have one visit that will take 3 4 hours. This will include:

 Medical and family history

 Eye exam: This includes the pupil being dilated.

 Electroretinography: A small electrode is taped to the forehead. Participants sit in the

 dark with their eyes patched for 30 minutes. Then numbing drops and contact lenses are put in

 the eyes. They will watch flashing lights.

 Blood tests

 Saliva sample: They will spit into a container or have the inside of their cheek swabbed.

 Genetic testing will be done on participants blood or saliva.

 Participants may meet with the researchers to discuss their genetic tests.
Objective: This project, Clinical and Molecular Studies in Families with Inherited Eye
 Disease will study inherited eye diseases, both Mendelian and complex age related inherited
 eye diseases, in families of many nationalities and ethnic backgrounds in order to identify
 the genes that, when mutated, cause inherited eye diseases and the pathophysiology through
 which they act. Among the diseases studied will be cataracts, corneal dystrophies and other
 corneal diseases, retinal degenerations, myopia and other anterior chamber defects, and
 glaucoma.

 Study Population: Families and individuals of many nationalities and ethnic backgrounds. We
 will study a maximum of 5,000 patients and family members.

 Design: The study consists of ascertaining individuals and especially families with multiple
 individuals, affected by both congenital and age related inherited eye diseases. These
 participants and their families will undergo detailed ophthalmological examinations to
 characterize their visual system and determine their affectation status. A blood sample will
 be collected from each individual for isolation of DNA and in some individuals for
 lymphoblastoid transformation to establish a renewable source of DNA. Linkage analysis,
 association analysis, physical mapping, and mutational screening will be carried out to
 identify the specific gene and the mutations in it that are associated with inherited eye
 disease in the family. Mutation screening may involve Sanger sequencing if a small number of
 candidate genes are identified, or whole genome or whole exome sequencing if more genes
 remain as viable candidates after the initial analysis. If necessary, the gene product will
 be characterized biochemically. Blood samples may also be used to complete analyses such as:
 hemoglobin A1c (HbA1c), fasting blood glucose, and glucose tolerance tests. The study will
 enroll participants at NEI and collaborating institutions.

 Outcome Measures: Linkage will be determined using the lod score method, association will be
 determined using standard statistical procedures to estimate p values, and mutations in
 specific genes will be assessed using a combination of residue conservation, blosum score,
 bioinformatic prediction of structural damage to the protein, and molecular modeling.
 Assessment of biochemical, metabolic, and physiological effects of these mutations will be
 individualized to the specific case.
-  INCLUSION CRITERIA:

 To be eligible, the following inclusion criteria must be met, where applicable;

 1. Participant must be four years of age or older.

 2. Participant must understand and sign the protocol s informed consent document.

 3. Individuals or family members of individuals with inherited eye diseases, either
 congenital, childhood, or age related.

 4. All participants must be able to cooperate with study examination and phlebotomy.

 EXCLUSION CRITERIA:

 A participant is not eligible if any of the following exclusion criteria are present:

 1. Participant has a disease, infection, or trauma that mimic inherited cataracts,
 retinal degenerations, glaucoma, etc.

 2. Participant has a significant active infection (an infection requiring treatment as
 determined by the investigator) or a history of chronic or recurrent infections.

 3. Participant requires sedation for study procedures.