Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy

Elliott H Sohn; Peter J Francis; Jacque L Duncan; Richard G Weleber; David A Saperstein; Donald F Farrell; Edwin M Stone

doi:10.1001/archophthalmol.2009.148

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Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy

Journal article

Open access

Peer reviewed

Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy

Elliott H Sohn, Peter J Francis, Jacque L Duncan, Richard G Weleber, David A Saperstein, Donald F Farrell and Edwin M Stone

Archives of ophthalmology (1960), Vol.127(7), pp.913-920

07/2009

DOI: 10.1001/archophthalmol.2009.148

PMCID: PMC2711525

PMID: 19597114

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Abstract

To study the phenotypic characteristics of patients with a novel p.E292K mutation in BEST1. Affected individuals underwent ophthalmic examination and testing that included photography, autofluorescence, optical coherence tomography, and electrophysiological testing. Their DNA was analyzed for BEST1 mutations. Five patients aged 5 to 59 years who expressed the p.E292K mutation in BEST1 were identified in 3 families. Electro-oculographic light-rise was subnormal in all probands and carriers. Carriers had normal findings from fundus examination, multifocal electroretinography, and visual acuity, and were emmetropic or myopic. Only probands had hyperopia and fundus findings typical of Best macular dystrophy. Optical coherence tomography of vitelliform lesions demonstrated retinal pigment epithelium elevation without subretinal fluid; atrophic lesions exhibited disruption of the hyperreflective outer retina-retinal pigment epithelium complex. Intense hyperautofluorescence correlated with the vitelliform lesion. Patients with the Glu292Lys variation in BEST1 exhibit intrafamilial and interfamilial phenotypic variability. A disproportionate fraction (26%) of Best disease-causing mutations occurs in exon 8, suggesting that the portion of protein encoded by this exon (amino acids 290-316) may be especially important to bestrophin's function. Relatively good visual acuity with vitelliform lesions can be explained by preservation of the outer retina, demonstrated by optical coherence tomography. Clinical Relevance A novel mutation in this region of BEST1 carries implications for disease pathogenesis.

Electrophysiology

Fluorescence

Photography

Phenotype

Electrooculography

Humans

Middle Aged

Child, Preschool

Male

Chloride Channels - genetics

Mutation, Missense

Macular Degeneration - diagnosis

Bestrophins

DNA Mutational Analysis

Adult

Female

Eye Proteins - genetics

Child

Tomography, Optical Coherence

Exons - genetics

Genotype

Point Mutation

Lysine - genetics

Macular Degeneration - genetics

Pedigree

Adolescent

Glutamine - genetics

Genetic Variation - genetics

Details

Title: Subtitle: Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy
Creators: Elliott H Sohn - Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA. elliott.sohn@gmail.com
Peter J Francis
Jacque L Duncan
Richard G Weleber
David A Saperstein
Donald F Farrell
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.127(7), pp.913-920
DOI: 10.1001/archophthalmol.2009.148
PMID: 19597114
PMCID: PMC2711525
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: EY002162 / NEI NIH HHS P30 EY002162-31 / NEI NIH HHS Howard Hughes Medical Institute P30 EY002162 / NEI NIH HHS
Language: English
Date published: 07/2009
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979933102771

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