Common and rare variants in patients with early onset drusen maculopathy

Anita de Breuk, Yara T. E. Lechanteur, Galuh Astuti, Jordi Corominas Galbany, Caroline C. W. Klaver, Carel B. Hoyng, Anneke I. den Hollander*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Downloads (Pure)


Early onset drusen maculopathy (EODM) can lead to advanced macular degeneration at a young age, affecting quality of life. However, the genetic causes of EODM are not well studied. We performed whole genome sequencing in 49 EODM patients. Common genetic variants were analysed by calculating genetic risk scores based on 52 age-related macular generation (AMD)-associated variants, and we analysed rare variants in candidate genes to identify potential deleterious variants that might contribute to EODM development. We demonstrate that the 52 AMD-associated variants contributed to EODM, especially variants located in the complement pathway. Furthermore, we identified 26 rare genetic variants predicted to be pathogenic based on in silico prediction tools or based on reported pathogenicity in literature. These variants are located predominantly in the complement and lipid metabolism pathways. Last, evaluation of 18 genes causing inherited retinal dystrophies that can mimic AMD characteristics, revealed 11 potential deleterious variants in eight EODM patients. However, phenotypic characteristics did not point towards a retinal dystrophy in these patients. In conclusion, this study reports new insights into rare variants that are potentially involved in EODM development, and which are relevant for future studies unravelling the aetiology of EODM.
Original languageEnglish
Pages (from-to)414-423
Number of pages10
JournalClinical Genetics
Issue number5
Early online date21 Aug 2022
Publication statusPublished - Nov 2022

Bibliographical note

Funding information
Bayer Ophthalmology Research Award (BORA); Dutch Research Council, Grant/Award
Number: 016.Vici.170.024

© 2022 The Authors.Clinical Geneticspublished by John Wiley & Sons Ltd.

Funding Information:
The authors would like to thank Corina Brussee, Ada Hooghart and Amal Hamimida for their contribution to grading of the retinal images, and Dr. Monés and Dr. Biarnés for their contributions in patient inclusion.

Funding Information:
This research was supported by the Dutch Research Council (016.Vici.170.024 to Anneke I. den Hollander) and by the Bayer Ophthalmology Research Award (BORA). The funding organizations had no role in the design or conduct of the study and were not involved in interpretation of the data or writing of the manuscript.

Publisher Copyright:
© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.


Dive into the research topics of 'Common and rare variants in patients with early onset drusen maculopathy'. Together they form a unique fingerprint.

Cite this