Ophthalmic Molecular Genetics

Objective To evaluate the molecular genetic defects associated with retinitispunctata albescens (RPA) in 5 patients from 3 families with this disease. Methods We examined 3 probands and 2 clinically affected relatives with RPA.Clinical examinations included best-corrected visual acuity, visual fieldtesting, electroretinography, dilated fundus examination, and fundus photography.Leukocyte DNA was analyzed for mutations in the exons of the genes encodingcellular retinaldehyde–binding protein 1 ( RLBP1 ),11- cis -retinol dehydrogenase ( RDH5 ), interphotoreceptor retinoid–binding protein ( RBP3 ), and photoreceptor all- trans -retinoldehydrogenase ( RDH8 ). Not all patients were evaluatedfor mutations in each gene. The exons were individually amplified and screenedfor mutations by single-stranded conformational polymorphism analysis or directgenomic sequencing. Results The 3 probands had similar clinical findings, including a history ofpoor night vision, the presence of punctate white deposits in the retina,and substantially reduced or absent rod responses on electroretinogram testing.One of the probands (patient 2:III:2) had 2 novel mutations in the RLBP1 gene (Arg151Trp and Gly31[2–base pair deletion], [GGA→G–]).Segregation analysis showed that the 2 mutations were allelic and that thepatient was a compound heterozygote. Both parents of the proband manifestedround white deposits in the retina. The other 2 probands had no detected pathogenicmutations in RLBP1 or in the other 3 genes evaluated. Conclusions The identification of novel RLBP1 mutationsin 1 of our 3 probands, all with RPA, is further evidence of genetic (nonallelic)heterogeneity in this disease. The presence of round white deposits in theretina may be observed in those heterozygous for RLBP1 . Clinical Relevance Patients with a clinical presentation of RPA can have genetically differentmutations. Drusen-like lesions may be observed in heterozygotes in familieswith this disease and a mutation in RLBP1 .