Search for mutations in the peropsin gene, an RPE–specific rhodopsin homolog, in patients with inherited retinal degeneration

Abstract

Abstract: : Purpose: To investigate the sequence of the peropsin gene, encoding a seven–transmembrane receptor of the rhodopsin family, for the presence of mutations possibly associated with retinitis pigmentosa or an allied disease. Methods: Leukocyte DNA samples from 207 unrelated patients with recessive retinitis pigmentosa (ARRP) and 52 patients with Leber congenital amaurosis (LCA) were used as templates to PCR–amplify the 7 exons of the peropsin gene and their immediate intronic sequences. The amplified sequences were evaluated for mutations using SSCP or direct sequencing. Results: Nine changes were detected. One of them, IVS5+8A>G, was found in 30 patients (29 heterozygotes and 1 homozygote) and appeared to be a nonpathogenic polymorphism. Another intron change, IVS5–5T>C, was present heterozygously in a patient with ARRP but was not considered to be pathogenic since it was predicted not to modify the correct splicing of exons 5 and 6. The isocoding change Leu153Leu was detected in 5 patients with ARRP (4 heterozygotes and 1 homozygote) and 3 heterozygous patients with LCA; another isocoding change, Thr174Thr, was detected in a homozygote and in 5 heterozygotes with ARRP and 5 heterozygotes with LCA. These variations also did not appear to alter the predicted splicing pattern of the peropsin mRNA. Two missense changes, Ser18Leu and Asp326Asn, were found heterozygously in one and 5 patients with ARRP, respectively, but they did not cosegregate with the disease in these families and therefore were considered nonpathogenic variants. Two other heterozygous missense changes, His211Arg and Pro274Ser, cosegregated with ARRP and LCA, respectively, in 3 families, however, sequencing of the entire gene did not reveal a 2^nd mutant allele, making it unlikely that these variations are pathogenic. Finally, a heterozygous frameshift mutation, Ile244(2–bp del, 1–bp ins) was detected in the only child, with ARRP, of a consanguineous marriage; no 2^nd mutant allele was found. Conclusions:At the present time there is no evidence that the peropsin gene causes ARRP or LCA. The evaluation of additional DNA samples from patients with other forms of retinal degeneration is currently underway.

Keywords: retinal degenerations: hereditary • gene screening • opsins