Purpose: The aim of this study was to analyze and report pathogenic variants in the ABCA4 gene in Brazilian patients with a clinical diagnosis of Stargardt disease.
Methods: This retrospective study evaluated variants in the ABCA4 gene in Brazilian patients with Stargardt disease. The patients' visual acuity and age of symptom onset were obtained from previous medical records. The patients were classified according to the autofluorescence patterns.
Results: Fifty patients aged between 10 and 65 years from 44 families were included in the study. Among these cases, the mean age of symptom onset was 14 years (range, 5-40 years). ABCA4 gene sequencing was conclusive in 40 patients (80%), negative in two patients (4%), and inconclusive in eight patients (16%). Four families carried homozygous pathogenic variants. Segregation analysis results were available for 23 families. One novel variant was found: p.Ala2084Pro. The most frequent pathogenic variant in this group was p.Arg602Trp (12/100 alleles). Based on the phenotypic characteristics assessed with fundus autofluorescence imaging, 12 patients were classified as having type I phenotype, 16 as having type II, and 18 patients as having type III. The cases classified as type III phenotype included patients who were homozygous for the p.Asn96Asp and p.Arg2030* variants. One patient with a type I phenotype carried the homozygous intronic variant c.3862+1G>A.
Conclusions: Next-generation sequencing was effective for the molecular diagnosis of genetic diseases and specifically allowed a conclusive diagnosis in 80% (40/50) of the patients. As the ABCA4 gene does not show a preferential region for pathogenic variants, the diagnosis of Stargardt disease depends on broader analysis of the gene. The most common pathogenic variants in the ABCA4 gene described in the literature were also found in these Brazilian patients. Although some genotype-phenotype correlations were found, more studies regarding the progression of Stargardt disease will help increase our understanding of the pathogenicity of these gene variants.