DNA LINKAGE STUDIES OF DEGENERATIVE RETINAL DISEASES

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DESCRIPTION: The purpose of this project is to determine the types and frequencies of genes causing autosomal dominant retinitis pigmentosa (ADRP) in an ethnically-diverse population from the Southwestern United States. ADRP is a complex set of diseases with multiple genetic causes. The investigators and others have identified at least eight genes or gene loci causing this condition. However, it is unlikely that this is the complete set of genes causing ADRP; further, the fraction of cases caused by each gene is largely unknown. The intent of this proposal is to systematically apply mutation screening and linkage testing to ADRP patients and families to establish useful estimates of the numbers and frequencies of the underlying disease genes within this community. As part of the investigators' ongoing research they collaborated in establishing the Southwest Eye Registry (SER) based in Dallas, Texas. SER is 1.) a list of participating retinal specialists in Texas, Oklahoma, Arkansas and Louisiana who treat patients with inherited retinal diseases and 2.) an encoded (non-confidential) list of patients seen by these clinicians. Currently, SER has registered more than 15 participating retinal specialists and 2,100 patients, including approximately 200 with ADRP. From this and other sources the investigators have identified 28 families suitable for mutation and linkage testing. Throughout the period of this proposal the investigators anticipate identifying a total of 70 to 80 families within Texas and bordering states. Mutation screening will be conducted by the Laboratory for the Molecular Diagnosis of Inherited Eye Diseases at UT- Houston. The investigators will test for mutations in rhodopsin, peripherin/RDS, ROM1 and other genes using single strand conformational analysis and genomic sequencing. If mutations are not found, then for patients with families suitable for linkage exclusion (7 or more potentially informative meioses) the investigators will test for linkage to microsatellite markers tightly linked to the known ADRP loci or related loci. If a family is large enough for linkage inclusion (10 or more potentially informative meioses), and if prior testing excludes the known loci, then the investigators will test for new ADRP loci using genome-wide linkage testing with a panel of microsatellite markers that span the human genome at 10 cM intervals. Finally, families showing linkage to a candidate gene will be screened for mutations in this gene. Delineation of the genes and mutations causing ADRP will be of direct benefit to patients for diagnosis and counseling, and will assist in rational planning of diagnostic services. In addition, this information will contribute to a better understanding of the molecular bases of these diseases. Finally, characterization of the genes causing retinitis pigmentosa and related conditions should assist in design of preventive therapies and treatments.