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Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene
Journal article   Open access   Peer reviewed

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene

G A Fishman, E M Stone, S Grover, D J Derlacki, H L Haines and R R Hockey
Archives of ophthalmology (1960), Vol.117(4), pp.504-510
04/1999
DOI: 10.1001/archopht.117.4.504
PMID: 10206579
url
https://doi.org/10.1001/archopht.117.4.504View
Published (Version of record) Open Access

Abstract

To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.
 Electroretinography Humans Middle Aged Male Sequence Analysis, DNA Genetic Variation Polymorphism, Single-Stranded Conformational Point Mutation ATP-Binding Cassette Transporters - genetics Macular Degeneration - genetics Pedigree Visual Fields Polymerase Chain Reaction Adult Female Aged Visual Field Tests Child Fluorescein Angiography Macular Degeneration - pathology

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