Phenotype-genotype correlations in patients with inherited ABCA4-associated retinal diseases

Abstract

The aim of this study was to characterize phenotype-genotype correlations in patients with ABCA4-associated IRDs. By NGS, we have identified the widespread “mild” ABCA4 mutation p.G1961E in 20 of 54 IRD patients with at least one mutation in the ABCA4 gene. In 8 patients, p.G1961E was in combination with a complex missense mutation p. [L541P; A1038V], in six - in combination with other missense mutations (p.N1805D; p.R1640W; p. P1088T; p.L541P; p.P1380L; p.R1640Q). In 81% of our patients with a disease course of 9 years or more, the p.G1961E mutation is associated with mild disease, even in the presence of a second severe mutation, and is a predictor of a milder phenotype, in accordance with the basic model of phenotype-genotype correlations in ABCA4-associated diseases.