Molecular analysis of the RPE65 gene in 72 Spanish families with autosomalrecessive retinitis pigmentosa

BACKGROUD: Autosomal recessive retinitis pigmentosa (arRP) is the most comm on form of retinitis pigmentosa CRP). It is characterized by a high degree of allelic and non-allelic genetic heterogeneity. Previously, it has been d emonstrated that the RPE65 gene is responsible for 2% recessive or isolated RP cases and 16% Leber's congenite amaurosis cases. Although the concrete function of RPE65 is unknown as yet, it has been found to be involved in vi tamin A metabolism and rhodopsin regeneration. PATIENTS AND METHOD: We studied the involvement of the RPE65 gene in 72 arR P Spanish families by means of indirect molecular and mutation analysis. RESULTS: The results obtained using the intragenic microsatellite marker D1 S2803 allowed us to exclude RPE65 as the causative gene of the disease in 8 0.5% of the families studied. Three new variants of the RPE65 gene have bee n identified: IVS6-43delA, IVS6-42delT and IVS6-33CG. We found that IVS6-33 C-->G was a common polymorphism. The other variants, namely IVS6-43delA and IVS6-42delT, were not identified in 150 control chromosomes studied. The s egregation analysis of IVS6-42delT variant seemed to exclude it as being in volved in the disease. CONCLUSIONS: Our results argue against the involvement of RPE65 gene in the families studied, indicating that the prevalence of RPE65 abnormalities in arRP Spanish families may be lower than that observed in other populations .