The hereditary macular degenerations encompass a large number of poorly understood and confusing group of diseases which cause impairment of central vision. Some of these maculopathies have a classical Mendelian inheritance pattern and are individually uncommon while other maculopathies, such as age-related maculopathy (ARM), apparently are genetically influenced (but with non-Mendelian inheritance) and are very common thus representing a major public health dilemma. It is these less common maculopathies with classical inheritance patterns which are more amenable to powerful molecular genetic approaches and more likely to unlock the basic mysteries of macular function and dysfunction. The understanding and knowledge gained from these rarer disorders, can then be applied to more common diseases such as age-related maculopathy. The overall approach will be to fully characterize one macular specific disease, denoted MCDR1, clinically, electrophysiologically, psychophysically and molecularly and investigate this gene's role in ARM as well as other maculopathies. Patients affected with the MCDR1 phenotype have many similarities to ARM with the exception of the earlier age of onset. Because of these similarities, the full characterization of MCDR1 will reveal insights into ARM and macular specific function. The PI has recently clarified the clinical understanding, classification and gene localization of MCDR1. The next step will be to identify the mutation causing MCDR1, this will involve using in concert several new techniques such as chromosomal micro-dissection, enrichment cloning of new genetic markers and selective hybridization cloning. Then a genotype to phenotype correlation will be made. The MCDR1 gene will be used as a candidate gene for other genetically influenced macular disorders such as ARM, cone degeneration macular colobomata and similar incurable diseases.
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