MUTATIONS IN THE RPE65 GENE IN PATIENTS WITH AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA OR LEBER CONGENITAL AMAUROSIS

RPE65 is a protein of unknown function expressed specifically by the r etinal pigment epithelium. We examined all 14 exons of this gene in 14 7 unrelated patients with autosomal recessive retinitis pigmentosa (RP ), in 15 patients with isolate RP, and in 45 patients with Leber conge nital amaurosis (LCA). Sequence anomalies that were likely to be patho genic were found in two patients with recessive RP, in one patient wit h isolate RP recategorized as recessive, and in seven patients with LC A. Cosegregation analysis in each available family showed that all aff ected individuals were either homozygotes or compound heterozygotes an d that all unaffected individuals were either heterozygote carriers or homozygous wild type, In one family, there was one instance of a new mutation not present in either parent of the affected individual, In a nother family, affected members with recessive RP in three branches (i .e., three distinct pairs of parents) were compound heterozygotes for the same two mutations or homozygous for one of them, Based on our res ults, mutations in the RPE65 gene appear to account for approximate to 2% of cases of recessive RP and approximate to 1.6% of cases of LCA.