title: Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens: evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes.
abstract: OBJECTIVE
  To evaluate the molecular genetic defects associated with retinitis punctata 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 field testing, electroretinography, dilated fundus examination, and fundus photography. Leukocyte DNA was analyzed for mutations in the exons of the genes encoding cellular retinaldehyde-binding protein 1 (RLBP1), 11-cis-retinol dehydrogenase (RDH5), interphotoreceptor retinoid-binding protein (RBP3), and photoreceptor all-trans-retinol dehydrogenase (RDH8). Not all patients were evaluated for mutations in each gene. The exons were individually amplified and screened for mutations by single-stranded conformational polymorphism analysis or direct genomic sequencing.
  
  
  RESULTS
  The 3 probands had similar clinical findings, including a history of poor 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 the patient was a compound heterozygote. Both parents of the proband manifested round white deposits in the retina. The other 2 probands had no detected pathogenic mutations in RLBP1 or in the other 3 genes evaluated.
  
  
  CONCLUSIONS
  The identification of novel RLBP1 mutations in 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 the retina may be observed in those heterozygous for RLBP1. Clinical Relevance Patients with a clinical presentation of RPA can have genetically different mutations. Drusen-like lesions may be observed in heterozygotes in families with this disease and a mutation in RLBP1.
authors.affiliation: Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of Illinois at Chicago, 60612, USA. gerafish@uic.edu
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Mary Flynn
authors.initials: MF
authors.lastname: Roberts
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Derlacki
authors.forename: Jonna L
authors.initials: JL
authors.lastname: Grimsby
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
authors.forename: Koji M
authors.initials: KM
authors.lastname: Nishiguchi
authors.forename: Thaddeus P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005654:Fundus Oculi; D018740:Genetic Heterogeneity; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D012160:Retina / Q000502:physiology; D012172:Retinaldehyde / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D012172:Retinaldehyde