Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration

Monica A. De La Paz, Vanessa K. Guy, Suzanne Abou-Donia, Ruth Heinis, Bekki Bracken, Jeffery M Vance, John Gilbert, J. Donald M Gass, Jonathan L. Haines, Margaret A Pericak-Vance

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Purpose: Age-related macular degeneration (AMD) is a complex genetic disorder and the leading cause of severe vision loss in the elderly. The Stargardt disease gene (ABCR) has been proposed as a major genetic risk factor in AMD. The purpose of this study was to evaluate the authors' AMD population for the specific ABCR variants proposed previously as genetic risk factors for AMD. Methods: The authors screened their AMD population (159 familial cases from 112 multiplex families and 53 sporadic cases) and 56 racially matched individuals with no known history of AMD from the same clinic population for evidence of the ABCR variants. Grading of disease severity was performed according to a standard protocol. Patients with extensive intermediate drusen or large soft drusen, drusenoid retinal pigment epithelial (RPE) detachments, geographic atrophy of the RPE, or evidence of exudative maculopathy were considered affected. Analysis for variants was performed by polymerase chain reaction amplification of individual exons of the ABCR gene with flanking primers and a combination of single-strand conformation polymorphism, heteroduplex analysis, and high-performance liquid chromatography. All abnormal conformers detected using these techniques were characterized by direct sequencing. Results: The authors identified only two of the previously reported variants in their study population. Both variants occurred in sporadic cases, and none was found in familial cases or the randomly selected population. In addition, the authors identified several newly described polymorphisms and variants in both the AMD and control populations. Conclusions: Based on these initial findings, the authors suggest that ABCR is not a major genetic risk factor for AMD in their study population. Additional genetic studies are needed to more fully evaluate the role of ABCR in AMD.

Original languageEnglish
Pages (from-to)1531-1536
Number of pages6
JournalOphthalmology
Volume106
Issue number8
StatePublished - Aug 1 1999
Externally publishedYes

Fingerprint

Macular Degeneration
Genes
Population
Geographic Atrophy
Heteroduplex Analysis
Stargardt disease 1
Inborn Genetic Diseases
Retinal Pigments
Retinal Detachment
Exons
High Pressure Liquid Chromatography
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Ophthalmology

Cite this

De La Paz, M. A., Guy, V. K., Abou-Donia, S., Heinis, R., Bracken, B., Vance, J. M., ... Pericak-Vance, M. A. (1999). Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. Ophthalmology, 106(8), 1531-1536.

Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. / De La Paz, Monica A.; Guy, Vanessa K.; Abou-Donia, Suzanne; Heinis, Ruth; Bracken, Bekki; Vance, Jeffery M; Gilbert, John; Gass, J. Donald M; Haines, Jonathan L.; Pericak-Vance, Margaret A.

In: Ophthalmology, Vol. 106, No. 8, 01.08.1999, p. 1531-1536.

Research output: Contribution to journalArticle

De La Paz, MA, Guy, VK, Abou-Donia, S, Heinis, R, Bracken, B, Vance, JM, Gilbert, J, Gass, JDM, Haines, JL & Pericak-Vance, MA 1999, 'Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration', Ophthalmology, vol. 106, no. 8, pp. 1531-1536.
De La Paz MA, Guy VK, Abou-Donia S, Heinis R, Bracken B, Vance JM et al. Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. Ophthalmology. 1999 Aug 1;106(8):1531-1536.
De La Paz, Monica A. ; Guy, Vanessa K. ; Abou-Donia, Suzanne ; Heinis, Ruth ; Bracken, Bekki ; Vance, Jeffery M ; Gilbert, John ; Gass, J. Donald M ; Haines, Jonathan L. ; Pericak-Vance, Margaret A. / Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. In: Ophthalmology. 1999 ; Vol. 106, No. 8. pp. 1531-1536.
@article{da8b34373b63436eb18c56be936f643d,
title = "Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration",
abstract = "Purpose: Age-related macular degeneration (AMD) is a complex genetic disorder and the leading cause of severe vision loss in the elderly. The Stargardt disease gene (ABCR) has been proposed as a major genetic risk factor in AMD. The purpose of this study was to evaluate the authors' AMD population for the specific ABCR variants proposed previously as genetic risk factors for AMD. Methods: The authors screened their AMD population (159 familial cases from 112 multiplex families and 53 sporadic cases) and 56 racially matched individuals with no known history of AMD from the same clinic population for evidence of the ABCR variants. Grading of disease severity was performed according to a standard protocol. Patients with extensive intermediate drusen or large soft drusen, drusenoid retinal pigment epithelial (RPE) detachments, geographic atrophy of the RPE, or evidence of exudative maculopathy were considered affected. Analysis for variants was performed by polymerase chain reaction amplification of individual exons of the ABCR gene with flanking primers and a combination of single-strand conformation polymorphism, heteroduplex analysis, and high-performance liquid chromatography. All abnormal conformers detected using these techniques were characterized by direct sequencing. Results: The authors identified only two of the previously reported variants in their study population. Both variants occurred in sporadic cases, and none was found in familial cases or the randomly selected population. In addition, the authors identified several newly described polymorphisms and variants in both the AMD and control populations. Conclusions: Based on these initial findings, the authors suggest that ABCR is not a major genetic risk factor for AMD in their study population. Additional genetic studies are needed to more fully evaluate the role of ABCR in AMD.",
author = "{De La Paz}, {Monica A.} and Guy, {Vanessa K.} and Suzanne Abou-Donia and Ruth Heinis and Bekki Bracken and Vance, {Jeffery M} and John Gilbert and Gass, {J. Donald M} and Haines, {Jonathan L.} and Pericak-Vance, {Margaret A}",
year = "1999",
month = "8",
day = "1",
language = "English",
volume = "106",
pages = "1531--1536",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration

AU - De La Paz, Monica A.

AU - Guy, Vanessa K.

AU - Abou-Donia, Suzanne

AU - Heinis, Ruth

AU - Bracken, Bekki

AU - Vance, Jeffery M

AU - Gilbert, John

AU - Gass, J. Donald M

AU - Haines, Jonathan L.

AU - Pericak-Vance, Margaret A

PY - 1999/8/1

Y1 - 1999/8/1

N2 - Purpose: Age-related macular degeneration (AMD) is a complex genetic disorder and the leading cause of severe vision loss in the elderly. The Stargardt disease gene (ABCR) has been proposed as a major genetic risk factor in AMD. The purpose of this study was to evaluate the authors' AMD population for the specific ABCR variants proposed previously as genetic risk factors for AMD. Methods: The authors screened their AMD population (159 familial cases from 112 multiplex families and 53 sporadic cases) and 56 racially matched individuals with no known history of AMD from the same clinic population for evidence of the ABCR variants. Grading of disease severity was performed according to a standard protocol. Patients with extensive intermediate drusen or large soft drusen, drusenoid retinal pigment epithelial (RPE) detachments, geographic atrophy of the RPE, or evidence of exudative maculopathy were considered affected. Analysis for variants was performed by polymerase chain reaction amplification of individual exons of the ABCR gene with flanking primers and a combination of single-strand conformation polymorphism, heteroduplex analysis, and high-performance liquid chromatography. All abnormal conformers detected using these techniques were characterized by direct sequencing. Results: The authors identified only two of the previously reported variants in their study population. Both variants occurred in sporadic cases, and none was found in familial cases or the randomly selected population. In addition, the authors identified several newly described polymorphisms and variants in both the AMD and control populations. Conclusions: Based on these initial findings, the authors suggest that ABCR is not a major genetic risk factor for AMD in their study population. Additional genetic studies are needed to more fully evaluate the role of ABCR in AMD.

AB - Purpose: Age-related macular degeneration (AMD) is a complex genetic disorder and the leading cause of severe vision loss in the elderly. The Stargardt disease gene (ABCR) has been proposed as a major genetic risk factor in AMD. The purpose of this study was to evaluate the authors' AMD population for the specific ABCR variants proposed previously as genetic risk factors for AMD. Methods: The authors screened their AMD population (159 familial cases from 112 multiplex families and 53 sporadic cases) and 56 racially matched individuals with no known history of AMD from the same clinic population for evidence of the ABCR variants. Grading of disease severity was performed according to a standard protocol. Patients with extensive intermediate drusen or large soft drusen, drusenoid retinal pigment epithelial (RPE) detachments, geographic atrophy of the RPE, or evidence of exudative maculopathy were considered affected. Analysis for variants was performed by polymerase chain reaction amplification of individual exons of the ABCR gene with flanking primers and a combination of single-strand conformation polymorphism, heteroduplex analysis, and high-performance liquid chromatography. All abnormal conformers detected using these techniques were characterized by direct sequencing. Results: The authors identified only two of the previously reported variants in their study population. Both variants occurred in sporadic cases, and none was found in familial cases or the randomly selected population. In addition, the authors identified several newly described polymorphisms and variants in both the AMD and control populations. Conclusions: Based on these initial findings, the authors suggest that ABCR is not a major genetic risk factor for AMD in their study population. Additional genetic studies are needed to more fully evaluate the role of ABCR in AMD.

UR - http://www.scopus.com/inward/record.url?scp=12944255842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12944255842&partnerID=8YFLogxK

M3 - Article

C2 - 10442900

AN - SCOPUS:12944255842

VL - 106

SP - 1531

EP - 1536

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

IS - 8

ER -