Abstract
Retinitis pigmentosa (RP) is a disease characterized by its vast heterogeneity. Many genes are associated with RP, and the disease causing mutations identified in these genes are even more numerous. To date there are 15 genes that cause autosomal dominant RP (adRP) alone. The role of some of these genes, while complex and not completely understood, is somewhat intuitive in that they are involved in pathways such as phototransduction. However, the role of other genes in retinal disease is not as predictable due to their ubiquitous function and/or expression. One such gene is inosine monophosphate dehydrogenase 1 (IMPDH1) IMPDH1 is a gene involved in de novo purine synthesis and is ubiquitously expressed. IMPDH1 mutations account for 2% of all adRP cases and are a rare cause of Leiber Congenital Amaurosis. Despite its ubiquitous expression missense mutations in this gene cause only retinal degeneration. This paradox of tissue specific disease in the presence of ubiquitous expression has only recently begun to be explained. We have shown in a recent study that novel retinal isoforms of IMPDH1 exist and may account for the tissue specificity of disease. We have gone on to characterize these retinal isoforms both in our laboratory and in collaboration with Dr. Lizbeth Hedstrom's laboratory at Brandeis University (Waltham, MA) in order to understand more about them. We believe that through clarifying the mechanism of disease in RP10 we will be equipped to consider treatment options for this disease.