Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease

Investigative Ophthalmology & Visual Science
Fabian GarcesRobert S Molday

Abstract

Stargardt disease (STGD1), the most common early-onset recessive macular degeneration, is caused by mutations in the gene encoding the ATP-binding cassette transporter ABCA4. Although extensive genetic studies have identified more than 1000 mutations that cause STGD1 and related ABCA4-associated diseases, few studies have investigated the extent to which mutations affect the biochemical properties of ABCA4. The purpose of this study was to correlate the expression and functional activities of missense mutations in ABCA4 identified in a cohort of Canadian patients with their clinical phenotype. Eleven patients from British Columbia were diagnosed with STGD1. The exons and exon-intron boundaries were sequenced to identify potential pathologic mutations in ABCA4. Missense mutations were expressed in HEK293T cells and their level of expression, retinoid substrate binding properties, and ATPase activities were measured and correlated with the phenotype of the STGD1 patients. Of the 11 STGD1 patients analyzed, 7 patients had two mutations in ABCA4, 3 patients had one detected mutation, and 1 patient had no mutations in the exons and flanking regions. Included in this cohort of patients was a severely affected 11-year-old child who wa...Continue Reading

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Jan 11, 2019·Biochemical Society Transactions·Robert C Ford, Konstantinos Beis
Nov 27, 2019·Genes·Anna M TracewskaKrystyna H Chrzanowska
Dec 2, 2020·Acta Ophthalmologica·Josephine Prener HoltanRagnheiður Bragadóttir
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Jul 24, 2021·American Journal of Ophthalmology·Etienne M SchönbachUNKNOWN ProgStar Study Group
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Oct 10, 2021·Nature Communications·Jessica Fernandes ScortecciRobert S Molday
Oct 15, 2021·The Journal of General Physiology·Daniel T InfieldNael A McCarty

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Methods Mentioned

BETA
transfection
Assay
electrophoresis
confocal scanning microscopy
protein folding

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