RRH, encoding the RPE-expressed opsin-like peropsin, is not mutated in retinitis pigmentosa and allied diseases.

Many genes from retinoid metabolism cause retinitis pigmentosa. Peropsin, an opsin-like protein with unknown function, is specifically expressed in apical retinal pigment epithelium microvilli. Since rhodopsin and RGR, another opsin-like protein, cause retinitis pigmentosa, we used D-HPLC to screen for the peropsin gene RRH in 331 patients (288 with retinitis pigmentosa and 82 with other retinal dystrophies). We found 13 nonpathogenic variants only, among which a c.730_731delATinsG that truncates the last two transmembrane-spanning fragments and the Lys284 required for retinol binding, but does not segregate with the disease phenotype. We conclude that RRH is not a frequent gene in retinitis pigmentosa.

Screening genes of the retinoid metabolism: novel LRAT mutation in leber congenital amaurosis.

PURPOSE: To evaluate the mutation prevalence and phenotype in genes involved in the ocular retinoid metabolism. DESIGN: We analyzed LRAT, encoding the lecithin retinol acyltransferase, and RDH10, a retinal pigment epithelium-specific retinol dehydrogenase. METHODS: We screened by denaturing-high performance liquid chromatography (D-HPLC) and direct sequencing all coding exons of LRAT and RDH10 in 216 patients, including 134 with simplex or multiplex retinitis pigmentosa and 82 with various types of flecked retinal dystrophies. RESULTS: Only nonpathogenic variants were found in this series. In an additional 2.5-year-old patient presenting with an "RPE65" phenotype (night blindness, photoattractivity, and visual improvement several months after birth), we discovered a homozygous deletion in LRAT (c.217_218delAT) leading to a premature stop at codon 120. CONCLUSIONS: The phenotype of patients with mutations in LRAT is similar to that of patients with mutations in RPE65, suggesting the need to systematically screen both genes in case of typical phenotype.

Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens.

PURPOSE: Retinitis punctata albescens (RPA) is an infrequently occurring form of autosomal recessive (and rarely dominant) retinal dystrophy featuring early-onset severe night blindness and tiny, dotlike, white deposits in the fundus. RPA is associated mostly with mutations in RLBP1 and occasionally in RHO, RDS, and RDH5. In this study, mutations were sought in RLBP1, which encodes the retinol binding protein CRALBP in patients with typical RPA. METHODS: Clinical investigation included funduscopy, visual field testing, electroretinogram recording, and adaptometry. The 7 coding exons (3-9) of RLBP1 and the 15th (last) exon of ABDH2 were PCR amplified and sequenced. Long-distance PCR and cloning of genomic DNA were performed to characterize the deletion. RESULTS: The study involved a 24-year-old Moroccan patient with typical RPA, born of first-cousin parents. He carried a 7.36-kb homozygous deletion encompassing the last 3 exons of RLBP1 (7, 8, and 9) and part of the intergenic region between RLBP1 and ABHD2, which lies downstream of RLBP1. This deletion abolishes the retinal binding site of CRALBP. The telomeric breakpoint of the deletion (in RLBP1 intron 6) is embedded in an Alu element, whereas the centromeric breakpoint (in the intergenic region) lies between two Alu elements placed in the opposite orientation. CONCLUSIONS: Because of the high density of Alu elements in RLBP1, a systematic search should be made for deletions in this gene when one or both alleles lack point mutations, in the case of RPA or flecked retinal dystrophy.