Correlation of clinical and genetic findings in Hungarian patients with Stargardt disease

PURPOSE. Autosomal recessive Stargardt disease (arSTGD) presents with substantial clinical and genetic heterogeneity. This study was conducted to correlate foveolar thickness (FT) and total macular volume (TMV), measured by optical coherence tomography (OCT), with other clinical characteristics and with specific genetic variation in Hungarian patients with arSTGD. METHODS. After a standard ophthalmic workup, both eyes of 35 patients with STGD from Hungary and of 25 age-matched healthy control subjects were tested with OCT. FT and TMV were measured automatically with the OCT mapping software in the nine Early Treatment Diabetic Retinopathy Study areas of 3500 mu m in diameter. All patients were screened for mutations by a combination of the ABCR400 microarray and direct sequencing. RESULTS. The patients with STGD presented with markedly thinned retina in the foveola and decreased macular volume, 72 mu m and 1.69 mm(3), respectively, compared with 169 mu m and 2.48 mm3 in the normal subjects, respectively. Statistically significant correlation was observed between visual acuity (VA) and TMV and between VA and FT. Disease-associated mutations were detected in 23 (65.7%) of 35 patients, including 48.5% with both alleles and 17.2% with one allele. The most frequent ABCA4 alleles in Hungarian patients with STGD were L541P/A1038V (in 28% of all patients), G1961E (20%) and IVS40+5G-->A (17%). Specific genotypes correlated with some phenotypic features and allowed for predictions of the disease progression. CONCLUSIONS. Hungarian patients with STGD presented with extensive foveolar thinning and macular volume loss. Genetic analysis detected several ABCA4 alleles at high frequency in the cohort of patients, suggesting founder effect(s). Unusually homogeneous distribution of disease-associated mutations aided genotype-phenotype correlation analyses in this population.