RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression

Samuel G Jacobson; Artur V Cideciyan; Tomas S Aleman; Alexander Sumaroka; Sharon B Schwartz; Elizabeth A M Windsor; Alejandro J Roman; Elise Heon; Edwin M Stone; Debra A Thompson

doi:10.1167/iovs.06-0599

Back

RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression

Journal article

Peer reviewed

RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression

Samuel G Jacobson, Artur V Cideciyan, Tomas S Aleman, Alexander Sumaroka, Sharon B Schwartz, Elizabeth A M Windsor, Alejandro J Roman, Elise Heon, Edwin M Stone and Debra A Thompson

Investigative ophthalmology & visual science, Vol.48(1), pp.332-338

01/2007

DOI: 10.1167/iovs.06-0599

PMID: 17197551

View Online

Abstract

Human blindness caused by mutation of visual cycle genes has been discussed as potentially treatable by retinoid replacement either through gene transfer or pharmacological bypass. Mutations in the RDH12 gene disrupt the visual cycle in vitro, but little is known of the in vivo effects of mutant RDH12, other than the association with severe early-onset autosomal recessive retinal disease. The relationship of retinal organization and visual function in patients with RDH12 mutations was determined and comparisons made with the disease from mutations in another visual cycle gene, RPE65. Young patients with RDH12 mutations were studied with optical coherence tomography (OCT) and colocalized measures of vision with dark-adapted absolute thresholds. Results were compared to those in patients with RPE65 mutations. Retinal architecture of patients with RDH12 mutations was appreciably distorted, precluding identification of the normal laminae. Some RDH12-mutant retinas were remarkably thick and others were thin, but all had the same dysplastic pattern. A comparison with the structural and functional consequences in patients with mutations in RPE65 indicated that the pathogenesis of retinal degeneration in RDH12 mutations was distinctly different. The results demand critical consideration of the human disease mechanism and the therapeutic approach in patients with mutations in the putative visual cycle gene RDH12.

Retinal Degeneration - diagnosis

Membrane Proteins - genetics

Retinal Degeneration - genetics

Tomography, Optical Coherence

Humans

Middle Aged

Psychophysics

Nerve Tissue Proteins - genetics

Alcohol Oxidoreductases - genetics

Dark Adaptation

Carrier Proteins - genetics

Vision, Ocular

Adolescent

Adult

Blindness - congenital

Eye Proteins - genetics

Mutation

Child

Retina - pathology

cis-trans-Isomerases

Details

Title: Subtitle: RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression
Creators: Samuel G Jacobson - Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. jacobsos@mail.med.upenn.edu
Artur V Cideciyan
Tomas S Aleman
Alexander Sumaroka
Sharon B Schwartz
Elizabeth A M Windsor
Alejandro J Roman
Elise Heon
Edwin M Stone
Debra A Thompson
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.48(1), pp.332-338
DOI: 10.1167/iovs.06-0599
PMID: 17197551
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Language: English
Date published: 01/2007
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980009702771

Metrics

18 Record Views

64 Times Cited - Web of Science

See more details