Fritsche, Lars G. and Fleckenstein, Monika and Fiebig, Britta S. and Schmitz-Valckenberg, Steffen and Bindewald-Wittich, Almut and Keilhauer, Claudia N. and Renner, Agnes B. and Mackensen, Friederike and Moessner, Andreas and Pauleikhoff, Daniel and Adrion, Christine and Mansmann, Ulrich and Scholl, Hendrik P. N. and Holz, Frank G. and Weber, Bernhard H. F. (2012) A Subgroup of Age-Related Macular Degeneration is Associated With Mono-Allelic Sequence Variants in the ABCA4 Gene. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 53 (4). pp. 2112-2118. ISSN 0146-0404,
Full text not available from this repository. (Request a copy)Abstract
PURPOSE. Age-related macular degeneration (AMD) is a heterogeneous condition of high prevalence and complex etiology involving genetic as well as environmental factors. By fundus autofluorescence (FAF) imaging, AMD can be classified into several distinct phenotypes, with one subgroup characterized by fine granular pattern with peripheral punctate spots (GPS[+]). Some features of GPS[+] overlap with Stargardt disease (STGD1), a recessive macular dystrophy caused by biallelic sequence variants in the ATP-binding cassette transporter 4 (ABCA4) gene. The aim of this study was to investigate the role of ABCA4 in GPS[+]. METHODS. The ABCA4 gene was sequenced in 25 patients with the GPS[+] phenotype and 29 with geographic atrophy (GA)-AMD but no signs of GPS (GPS[-]). In addition, frequencies of risk-increasing alleles at three known AMD susceptibility loci, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and complement component 3 (C3), were evaluated. RESULTS. We demonstrate that GPS[+] is associated significantly with monoallelic ABCA4 sequence variants. Moreover, frequencies of AMD risk-increasing alleles at CFH, ARMS2, and C3 are similar in GPS[+] and STGD1 patients, with risk allele frequencies in both subcategories comparable to population-based control individuals estimated from 3,510 individuals from the NHLBI Exome Sequencing Project. CONCLUSIONS. Our data suggest that the GPS[+] phenotype is accounted for by monoallelic variants in ABCA4 and unlikely by the well-established AMD risk-increasing alleles at CFH, ARMS2, and C3. These findings provide support for a complex role of ABCA4 in the etiology of a minor proportion of patients with AMD. (Invest Ophthalmol Vis Sci. 2012;53:2112-2118) DOI:10.1167/iovs.11-8785
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPLEMENT FACTOR-H; FUNDUS AUTOFLUORESCENCE PATTERNS; STARGARDT-DISEASE; GEOGRAPHIC ATROPHY; MISSENSE MUTATIONS; TRANSPORTER GENE; RISK; PROGRESSION; LIPOFUSCIN; DYSTROPHY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 May 2020 05:23 |
| Last Modified: | 15 May 2020 05:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18913 |
Actions (login required)
 |
View Item |
