Genotype-Phenotype Association in ABCA4-Associated Retinopathy

Maximilian Pfau; Wadih M Zein; Laryssa A Huryn; Catherine A Cukras; Brett G Jeffrey; Robert B Hufnagel; Brian P Brooks

doi:10.1007/978-3-031-27681-1_42

Genotype-Phenotype Association in ABCA4-Associated Retinopathy

Adv Exp Med Biol. 2023:1415:289-295. doi: 10.1007/978-3-031-27681-1_42.

Authors

Maximilian Pfau¹, Wadih M Zein¹, Laryssa A Huryn¹, Catherine A Cukras¹, Brett G Jeffrey¹, Robert B Hufnagel¹, Brian P Brooks²

Affiliations

¹ National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
² National Eye Institute, National Institutes of Health, Bethesda, MD, USA. brooksb@nei.nih.gov.

PMID: 37440047
DOI: 10.1007/978-3-031-27681-1_42

Abstract

Stargardt disease (STGD1) is the most common inherited retina degeneration. It is caused by biallelic ABCA4 variants, and no treatment is available to date. STGD1 shows marked phenotypic variability, especially regarding the age of onset. The underlying genotype can partially explain this variability. Notably, a subset of ABCA4 variants was previously associated with an earlier disease onset than truncating ABCA4 variants, pointing toward pathogenic mechanisms beyond the loss of gene function in these patients. On the other end of the spectrum, variants such as p.Gly1961Glu were associated with markedly slower extrafoveal disease progression. Given that these drastic differences in phenotype are based on genotype (resulting in important prognostic implications for patients), this chapter reviews previous approaches to genotype-phenotype correlation analyses in STGD1.

Keywords: ABCA4-associated retinopathy; Disease Progression; Genotype; Genotype–Phenotype correlation; Stargardt disease.

MeSH terms

ATP-Binding Cassette Transporters / genetics
Genetic Association Studies
Genotype
Humans
Macular Degeneration* / genetics
Macular Degeneration* / pathology
Mutation
Phenotype
Stargardt Disease

Substances

ATP-Binding Cassette Transporters
ABCA4 protein, human