Photoreceptor function in heterozygotes with insertion or deletion mutations in the RDS gene

Samuel G Jacobson; Artur V Cideciyan; Colin M Kemp; Val C Sheffield; Edwin M Stone

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Photoreceptor function in heterozygotes with insertion or deletion mutations in the RDS gene

Journal article

Peer reviewed

Photoreceptor function in heterozygotes with insertion or deletion mutations in the RDS gene

Samuel G Jacobson, Artur V Cideciyan, Colin M Kemp, Val C Sheffield and Edwin M Stone

Investigative ophthalmology & visual science, Vol.37(8), pp.1662-1674

07/1996

PMID: 8675410

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Abstract

To understand the pathophysiology of human retinal degenerations caused by mutations in the peripherin/RDS gene. Three families with autosomal dominant retinal degeneration were found to have mutations in the peripherin/RDS gene. There were two frameshift mutations: a 1-base pair (bp) insertion at codon 32 and a 2-bp deletion at codon 193. For these mutations, the predicted proteins would be truncated by 303 and 131 amino acids, respectively. The third mutation would result in an 8-bp substitution for five nucleotides involving codons 67-69 and would be predicted to disrupt the second transmembrane domain of the protein. Heterozygotes were examined clinically and with rod and cone perimetry, dark adaptometry, and rod- and cone-isolated electroretinograms (ERGs). Rod and cone sensitivity losses were present with perimetric testing in most patients; patients with advanced disease in all three families showed more pericentral than peripheral field dysfunction. The kinetics of dark adaptation were abnormal in all patients. Rod and cone ERG a-waves were normal in maximum amplitude in three younger patients but were reduced in all others; phototransduction was normal in most patients. There was equal loss of rod and cone a-wave amplitudes and equal elevation of rod and cone thresholds. Heterozygotes with these different peripherin/RDS gene mutations showed variation in clinical presentation but a similar pattern of receptor abnormalities. Results of visual function tests were consistent with a normal amount of rod and cone outer segment membrane in early disease, progressing to reduced outer segments at later stages. There was an equal effect on rod and cone photoreceptor function at all stages of disease. This functional phenotype may represent the human analogue of the rds/+ mouse.

Signal Transduction

Sequence Deletion

Frameshift Mutation

Humans

Middle Aged

Molecular Sequence Data

Male

Dark Adaptation

DNA - analysis

Base Sequence

Intermediate Filament Proteins - genetics

Adult

Female

Eye Proteins - genetics

Membrane Glycoproteins

Electroretinography

Amino Acid Sequence

Peripherins

Retinal Degeneration - genetics

Nerve Tissue Proteins

Retinal Degeneration - physiopathology

Photoreceptor Cells - physiopathology

Pedigree

Adolescent

Heterozygote

Aged

Mutagenesis, Insertional

Visual Field Tests

Photoreceptor Cells - physiology

Details

Title: Subtitle: Photoreceptor function in heterozygotes with insertion or deletion mutations in the RDS gene
Creators: Samuel G Jacobson - Department of Ophthalmology, University of Pennsylvania School of Medicine, Scheie Eye Institute, Philadelphia 19104, USA
Artur V Cideciyan
Colin M Kemp
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.37(8), pp.1662-1674
PMID: 8675410
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: EY05627 / NEI NIH HHS EY08426 / NEI NIH HHS
Language: English
Date published: 07/1996
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979924102771

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