Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene

Samuel G Jacobson; Artur V Cideciyan; Yijun Huang; David B Hanna; Carole L Freund; Louisa M Affatigato; Ronald E Carr; Donald J Zack; Edwin M Stone; Roderick R McInnes

Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene

Journal article

Peer reviewed

Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene

Samuel G Jacobson, Artur V Cideciyan, Yijun Huang, David B Hanna, Carole L Freund, Louisa M Affatigato, Ronald E Carr, Donald J Zack, Edwin M Stone and Roderick R McInnes

Investigative ophthalmology & visual science, Vol.39(12), pp.2417-2426

11/1998

PMID: 9804150

View Online

Abstract

To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor-specific transcription factor. Heterozygotes with the E168 [delta1 bp], E168 [delta2 bp], or G217 [delta1 bp] CRXgene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT). Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [delta1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [delta2 bp], G217 [delta1 bp] mutations). In the family with the E168 [delta1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone-isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [delta1 bp] mutation) and two other patients (representing E168 [delta2 bp] and G217 [delta1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery. Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.

Mutation

Phenotype

Psychophysics

Electroretinography

Retinal Degeneration - genetics

Humans

Middle Aged

Retinal Degeneration - physiopathology

Visual Acuity

Photoreceptor Cells, Vertebrate - physiology

Homeodomain Proteins - genetics

Pedigree

Visual Fields

Trans-Activators - genetics

Tomography

Adult

Female

Visual Field Tests

Child

Details

Title: Subtitle: Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene
Creators: Samuel G Jacobson - Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA
Artur V Cideciyan
Yijun Huang
David B Hanna
Carole L Freund
Louisa M Affatigato
Ronald E Carr
Donald J Zack
Edwin M Stone
Roderick R McInnes
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.39(12), pp.2417-2426
PMID: 9804150
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: EY-01765 / NEI NIH HHS EY-09769 / NEI NIH HHS EY-05627 / NEI NIH HHS
Language: English
Date published: 11/1998
Academic Unit: The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979909602771

Metrics

20 Record Views

108 Times Cited - Web of Science