Objective: This project, Clinical and Molecular Studies in Families with Glaucoma and Related Diseases, will study the inheritance of glaucoma in families of many nationalities and ethnic backgrounds in order to identify the genes that, when mutated, cause glaucoma, elevated intraocular pressure, or similar diseases and the pathophysiology through which they act.
Study Population: The number of subjects to be enrolled has no logical upper limit, but will be at least 250 and not more than 2000 during the next 5 years.
Design: The study consists of ascertaining individuals and especially families with multiple individuals, affected by glaucoma or related retinal and anterior chamber diseases. These patients and their families will undergo detailed ophthalmological examinations and, where indicated, additional non-investigational examinations to characterize disease in their families and determine their affectation status. A blood sample will be collected from each individual for isolation of DNA and in some individuals biochemical testing or for lymphoblastoid transformation to establish a renewable source of DNA. Linkage analysis, physical mapping, SNP and microsatellite analysis for association studies, and mutational screening will be carried out to identify the specific the gene and the mutations in it that are associated with glaucoma in this family. If necessary, the gene product or blood sample will be characterized biochemically. The study will enroll subjects at the NEI and at collaborating institutions.
Outcome Measures: Linkage will be determined using the lod score method and mutations in specific genes will be assessed using a combination of residue conservation, blosum score, and molecular modeling. Biochemical, metabolic, and physiological effects will be individualized to the specific assay.
