Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023:1415:289-295.
doi: 10.1007/978-3-031-27681-1_42.

Genotype-Phenotype Association in ABCA4-Associated Retinopathy

Maximilian Pfau  1 , Wadih M Zein  1 , Laryssa A Huryn  1 , Catherine A Cukras  1 , Brett G Jeffrey  1 , Robert B Hufnagel  1 , Brian P Brooks  2
Affiliations

Genotype-Phenotype Association in ABCA4-Associated Retinopathy

Maximilian Pfau et al. Adv Exp Med Biol. 2023.

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement The authors have declared that no conflict of interest exists.

References

    1. Hanany M, Rivolta C, Sharon D. Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases. Proc Natl Acad Sci U S A. 2020. Feb;117(5):2710–6. - PMC - PubMed
    1. Huang D, Heath Jeffery RC, Aung-Htut MT, McLenachan S, Fletcher S, Wilton SD, et al. Stargardt disease and progress in therapeutic strategies. Ophthalmic Genet. 2021. Aug;1–26. - PubMed
    1. Cremers FPM, Lee W, Collin RWJ, Allikmets R. Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations. Prog Retin Eye Res. 2020. Nov;79:100861. - PMC - PubMed
    1. Stargardt K Über familiäre, progressive Degeneration in der Maculagegend des Auges. Albr von Graefes Arch für Ophthalmol [Internet]. 1909;71(3):534–550. Available from:10.1007/BF01961301. - DOI
    1. Strauss RW, Kong X, Ho A, Jha A, West S, Ip M, et al. Progression of Stargardt disease as determined by fundus autofluorescence over a 12-month period: ProgStar report no. 11. JAMA Ophthalmol. 2019. Aug;137(10):1134–45. - PMC - PubMed

Substances

LinkOut - more resources