Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Neidhardt, J; Barthelmes, D; Farahmand, F; Fleischhauer, J C; Berger, W (2006). Different amino acid substitutions at the same position in rhodopsin lead to distinct phenotypes. Investigative Ophthalmology and Visual Science, 47(4):1630-1635.

Full text not available from this repository.

View at publisher

Abstract

PURPOSE: Identification of a novel rhodopsin mutation in a family with retinitis pigmentosa and comparison of the clinical phenotype to a known mutation at the same amino acid position. METHODS: Screening for mutations in rhodopsin was performed in 78 patients with retinitis pigmentosa. All exons and flanking intronic regions were amplified by PCR, sequenced, and compared to the reference sequence derived from the National Center for Biotechnology Information (NCBI, Bethesda, MD) database. Patients were characterized clinically according to the results of best corrected visual acuity testing (BCVA), slit lamp examination (SLE), funduscopy, Goldmann perimetry (GP), dark adaptometry (DA), and electroretinography (ERG). Structural analyses of the rhodopsin protein were performed with the Swiss-Pdb Viewer program available on-line (http://www.expasy.org.spdvbv/ provided in the public domain by Swiss Institute of Bioinformatics, Geneva, Switzerland). RESULTS: A novel rhodopsin mutation (Gly90Val) was identified in a Swiss family of three generations. The pedigree indicated autosomal dominant inheritance. No additional mutation was found in this family in other autosomal dominant genes. The BCVA of affected family members ranged from 20/25 to 20/20. Fundus examination showed fine pigment mottling in patients of the third generation and well-defined bone spicules in patients of the second generation. GP showed concentric constriction. DA demonstrated monophasic cone adaptation only. ERG revealed severely reduced rod and cone signals. The clinical picture is compatible with retinitis pigmentosa. A previously reported amino acid substitution at the same position in rhodopsin leads to a phenotype resembling night blindness in mutation carriers, whereas patients reported in the current study showed the classic retinitis pigmentosa phenotype. The effect of different amino acid substitutions on the three-dimensional structure of rhodopsin was analyzed by homology modeling. Distinct distortions of position 90 (shifts in amino acids 112 and 113) and additional hydrogen bonds were found. CONCLUSIONS: Different amino acid substitutions at position 90 of rhodopsin can lead to night blindness or retinitis pigmentosa. The data suggest that the property of the substituted amino acid distinguishes between the phenotypes.

Citations

16 citations in Web of Science®
21 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 03 Mar 2011
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Molecular Genetics
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2006
Deposited On:03 Mar 2011 12:36
Last Modified:27 Nov 2013 18:00
Publisher:Association for Research in Vision and Ophthalmology
ISSN:0146-0404
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1167/iovs.05-1317
PubMed ID:16565402

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page