HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-1717v1 49/9/4105    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zeitz, C. Articles by Berger, W. Search for Related Content PubMed PubMed Citation Articles by Zeitz, C. Articles by Berger, W.

Identification and Functional Characterization of a Novel Rhodopsin Mutation Associated with Autosomal Dominant CSNB

¹From the Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Zurich, Switzerland; the ²Institut de la Vision, INSERM (Institut National de la Santé et de la Recherche Médicale), Université Pierre et Marie Curie6, Paris, France; the ⁴Department of Vision Sciences, University of Alabama at Birmingham, Birmingham, Alabama; the ⁵Department of Ophthalmology, University Hospital Basel, Basel, Switzerland; the ⁶Department of Biology, ETH (Eidgenössische Technische Hochschule), Zurich, Switzerland; and the ⁷Swiss Epilepsy Centre, Zurich, Switzerland.

PURPOSE. Mutations in RHO, PDE6B, and GNAT1 can lead to autosomal dominant congenital stationary night blindness (adCSNB). The study was conducted to identify the genetic defect in a large Swiss family affected with adCSNB and to investigate the pathogenic mechanism of the mutation.

METHODS. Two affected cousins of a large Swiss family were examined clinically by standard methods: funduscopy, EOG, ERG, and dark adaptometry. Twelve family members were screened for mutations in RHO. The ability of mutant rhodopsin to activate transducin constitutively was monitored by measuring the catalytic exchange of bound GDP for radiolabeled [³⁵S]GTPS in transducin.

RESULTS. A novel mutation was identified in RHO (c.884C>T, p.Ala295Val) in patients with adCSNB. They had full vision under photopic conditions, showed no fundus abnormalities, revealed EOG results in the normal range, but presented night blindness with an altered scotopic ERG. In the presence of 11-cis retinal, the mutant rhodopsin is inactive, similar to wild-type, responding only when exposed to light. However, in the absence of 11-cis-retinal, unlike wild-type opsin, the mutant opsin constitutively activates transducin.

CONCLUSIONS. The study adds a fourth rhodopsin mutation associated with CSNB. Although the phenotype of autosomal dominant CSNB may vary slightly in patients showing mutations in RHO, PDE6B, or GNAT1, the disease course seems to be stationary with only scotopic vision being affected. The data indicate that the mutant opsin activates transducin constitutively, which is a consistent and common feature of all four CSNB-associated rhodopsin mutations reported to date.