Genotype‐phenotype correlations in Stargardt disease/ABCA4‐related retinopathy

Abstract

AbstractPurpose To investigate genotype‐phenotype correlations in patients with Stargardt Disease (STGD) / ABCA4‐related retinopathyMethods 195 patients diagnosed with STGD and harbouring ABCA4 variants were recruited. A detailed clinical history and examination were undertaken. Pattern and full‐field ERGs (PERG; ERG) were used to classify 175 patients into three groups (Lois et al. 1999); dysfunction confined to the macula; macular and cone ERG abnormality; and macular and both cone and rod abnormality. Patients were also grouped by genotype: G1 ‐ two null variants (N=9); G2 ‐ at least one null variant with or without missense variants (67); G 3 ‐ at least two missense variants (50); G 4 ‐ one missense variant (69).Results All G1 patients had a group 3 ERG. 26/58 G2 were in ERG group 1; 26/58 in Group 3. 24/47 G3 patients were ERG group 1; 7/47 group 2; and 16/47 in ERG group 3. 31/61 G4 patients were in ERG group 1; 5 in group 2; and 25/61 in group 3. Significant clinical differences were also observed between the genotypes.Conclusion Patients with two null ABCA4 variants had the most severe phenotype. In comparison, patients with two or more missense variants had a more variable phenotype and included many with normal full‐field ERGs. This large survey confirms previous suggestions based on smaller cohorts and individual families.