Aim Biallelic ABCC6 mutations cause pseudoxanthoma elasticum, a systemic disease characterised by calcification of elastic tissue and a specific retinal phenotype. In this study, we investigated if monoallelic ABCC6 mutations are also associated with retinal alterations.
Methods In this prospective, cross-sectional, monocentre case–control study, carriers of monoallelic ABCC6 mutations were investigated and compared with age-matched controls. The retinal phenotype was characterised using fundus photography, fundus autofluorescence, confocal near-infrared reflectance imaging, spectral domain optical coherence tomography and in selected cases late-phase indocyanine green angiography.
Results Thirty-eight subjects carrying monoallelic ABCC6 mutations (mean age 70.2 years, range 50–90, 26 female) were examined and compared with 77 age-matched controls (mean age 69.9 years, range 50–93, 43 female). Retinal alterations were more frequently found in carriers of monoallelic ABCC6 mutations compared with controls (50% vs 33.8%, p=0.107) with increasing prevalence at older age. Typical findings were peripapillary atrophy (37% vs 23%, p=0.184), pattern dystrophy-like changes (24% vs 12%, p=0.109), reticular pseudodrusen (21% vs 5%, p=0.019), small angioid streaks (8% vs 1%, p=0.105), choroidal neovascularisations and atrophic lesions (both 8% vs 0%, p=0.034). Late-phase indocyanine green angiography showed a reduced cyanescence centred to the posterior pole in 11 of 14 examined subjects with monoallelic ABCC6 mutations.
Conclusion The findings of this study indicate a possible ocular ABCC6 haploinsufficiency phenotype. Due to its late-onset and phenotypic similarities, misinterpretation as age-related macular degeneration is possible.
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MG and IW contributed equally
MG and IW are joint first authors.
Correction notice This article has been corrected since it was published Online First. Corresponding author email address has been updated from email@example.com to firstname.lastname@example.org. ORCID IDs have been added. Minor formatting has also been corrected.
Contributors Study concept and design: MG, IW and PCI. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: MG, IW and PCI. Critical revision of the manuscript for important intellectual content: JB, PLM, IF, DH, FGH and RPF.
Funding This work was supported by the ProRetina, Aachen, Germany; the German Research Foundation (MG, grant # GL920/1-1); and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Oxford, UK.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was in adherence with the Declaration of Helsinki. IRB approval (Ethikkommission, Medical Faculty, Rheinische Friedrich-Wilhelms-University Bonn, Germany).
Provenance and peer review Not commissioned; externally peer reviewed.
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