ABCMdb

ABCA4 p.Thr1519Arg

Predicted by SNAP2:	A: N (72%), C: N (66%), D: N (53%), E: N (72%), F: N (53%), G: N (61%), H: N (78%), I: N (66%), K: N (82%), L: N (61%), M: N (72%), N: N (78%), P: N (61%), Q: N (72%), R: N (72%), S: N (87%), V: N (72%), W: D (71%), Y: N (57%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: D, G: N, H: D, I: D, K: N, L: D, M: D, N: N, P: N, Q: N, R: N, S: N, V: N, W: D, Y: D,

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[hide] A subgroup of age-related macular degeneration is ... Invest Ophthalmol Vis Sci. 2012 Apr 30;53(4):2112-8. doi: 10.1167/iovs.11-8785. Print 2012 Apr. Fritsche LG, Fleckenstein M, Fiebig BS, Schmitz-Valckenberg S, Bindewald-Wittich A, Keilhauer CN, Renner AB, Mackensen F, Mossner A, Pauleikhoff D, Adrion C, Mansmann U, Scholl HP, Holz FG, Weber BH
A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene.
Invest Ophthalmol Vis Sci. 2012 Apr 30;53(4):2112-8. doi: 10.1167/iovs.11-8785. Print 2012 Apr., [PMID:22427542]

Abstract [show]
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.

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93 These patients were heterozygous for variants c.634C>T (p.R212C), c.4556C>G (p.T1519R), and c.6148G>C (p.V2050L), respectively. Login to comment
91 These patients were heterozygous for variants c.634C>T (p.R212C), c.4556C>G (p.T1519R), and c.6148G>C (p.V2050L), respectively. Login to comment