Improving personalised genetic counselling for ABCA4 -associated retinopathy: Updated recurrence risk estimates

Abstract

Stargardt disease type 1 (STGD1) is caused by biallelic pathogenic variants in ABCA4. These variants vary in their effect on the resulting protein and the disease phenotype. Not all variant combinations cause disease, which complicates the determination of the recurrence risk of STGD1. Previously, the recurrence risk of STGD1 was estimated by analyzing variants in patient data and using their population variant frequencies in which white patients are overrepresented. Furthermore, assuming that variant effects are independent of genetic ancestry, estimates were made for each gnomAD population. In this article, the effects of missing heritability, de novo variants, reduced penetrance of variants and sex/gender are incorporated and discussed.