gms | German Medical Science

25th Annual Meeting of the German Retina Society

German Retina Society

01.06. - 02.06.2012, Münster

A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene

Meeting Abstract

  • Monika Fleckenstein - Universitäts-Augenklinik Bonn
  • L.G. Fritsche - Institut für Humangenetik, Universität Regensburg
  • B.S. Fiebig - Institut für Humangenetik, Universität Regensburg
  • S. Schmitz-Valckenberg - Universitäts-Augenklinik Bonn
  • A. Bindewald-Wittich - Universitäts-Augenklinik Bonn
  • C.N. Keilhauer - Universitäts-Augenklinik Würzburg
  • A.B. Renner - Universitäts-Augenklinik Regensburg
  • F. Mackensen - Universitäts-Augenklinik Heidelberg
  • A. Moessner - Universitäts-Augenklinik Leipzig
  • D. Pauleikhoff - St. Franziskus-Hospital Münster
  • C. Adrion - Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie, LMU München
  • U. Mansmann - Universitäts-Augenklinik Bonn
  • H.P. Scholl - Wilmer Eye Institute, Johns Hopkins University, Baltimore, USA
  • F.G. Holz - Universitäts-Augenklinik Bonn
  • B.H. Weber - Institut für Humangenetik, Universität Regensburg

German Retina Society. 25th Annual Conference of the German Retina Society. Münster, 01.-02.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12rg36

doi: 10.3205/12rg36, urn:nbn:de:0183-12rg369

This is the translated version of the article.
The original version can be found at:

Published: May 30, 2012

© 2012 Fleckenstein et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Purpose: Age-related macular degeneration (AMD) is a heterogenous 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 patients 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: Here, we demonstrate that GPS[+] is significantly associated 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 fraction of AMD patients.