Screen of the human arrestin gene in patients with retinitis pigmentosa and Oguchi disease
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Purpose. Arrestin is a 48-kD protein found in rod photoreceptor cells that plays a role in the deactivation of rhodopsin. In Drosophila, null mutations in the arrestin gene result in a light-dependent photoreceptor degeneration. In humans, a null mutation in the arrestin gene has been found in some Japanese patients with Oguchi disease, a rare form of recessive congenital stationary night blindness. We have undertaken the screening of three patients with Oguchi disease of non-Japanese descent to determine whether they exhibit a mutation in the arrestin gene. Furthermore, we are screening patients with retinitis pigmentosa (RP) to ascertain whether mutations in the arrestin gene can result in a degenerative retinal disease as well. Methods. We are using single strand conformation polymorphism (SSCP) and direct sequencing to screen the entire coding region, including the splice donor and acceptor sites, of three patients with Oguchi disease, 188 patients with autosomal dominant RP, and 104 patients with autosomal recessive RP. Results. Complete SSCP analysis has been performed on all patients. Analysis in patients with Oguchi disease has revealed variant bands in exons 7, 8, and 11. Sequencing has thus far revealed that these patients do not have the published arrestin gene mutation. Direct sequencing of variant bands found in patients with RP has revealed rare silent variants at codons 31 (GGG to GGA), 67 (TGC to TGT), 107 (CTG to CTC) and 288 (CTG to TTG), as well as a frequent polymorphism at codon 163 (GCC vs. GCT). Fifteen variant bands remain to be sequenced. Conclusion. We have found variant bands in the arrestin gene in three patients with Oguchi disease which are in the process of being sequenced. To date, we have not found a mutation in the arrestin gene in patients with RP that could be construed to be responsible for the disease. However, sequencing of variant bands has not been fully completed.