Genotype-Phenotype Association in ABCA4-Associated Retinopathy

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


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


  • ATP-Binding Cassette Transporters
  • ABCA4 protein, human