RESUMO
The nuclear receptor protein NR2E3 is postulated to play an important role in rod and cone photoreceptor development. NR2E3 gene mutational analyses were carried out in 103 unrelated subjects with different retinal diseases. A total of 14 different sequence variants were identified, including 3 mutations, 6 rare sequence variants and five polymorphisms. One of three mutations is novel (a frameshift mutation: c.1034_1038del5bp). Five of the six rare sequence variants and one of the polymorphisms identified are novel. Splice prediction programs and functional splicing assays were performed to study three of these variants. The c.119-2 A>C mutant allele construction produces, in addition to the normal one, an abnormal transcript of 180 bp resulting from an aberrant splicing with skipping of exon 2 and the generation of a premature stop codon in exon 3. These experimental data confirm the splice predictions made by the computer programs. The obtained results reinforce the idea that NR2E3 gene is involved in several retinal diseases without a clear genotype-phenotype correlation.
