Understanding the genetic pathology of Stargardt disease: a review of current findings and challenges

ABSTRACT Introduction: Stargardt macular dystrophy (STGD1), an autosomal recessive disorder, is caused by genetic mutations affecting ATP-Binding Cassette, subfamily A, member 4 (ABCA4). The genetic pathology of STGD1 is complex. Over 1200 disease-causing ABCA4 mutations have been identified which vary in disease severity and geographic/ethnic frequency. Areas Covered: This article provides an introduction to STGD1 and its pathophysiology, including a summary of the normal visual cycle and a description of the ABCA4 protein. The current understanding of the genetic pathology of STGD1 is reviewed, including the relationship between STGD1 and similar diseases, genotype-phenotype correlations of ABCA4-associated retinopathy, types of disease-causing genetic variations, geographic/ethnic considerations, and gene therapy. Expert Opinion: In STGD1, ABCA4 gene mutations and gene variation combinations in individuals can be used to predict phenotype, and can be categorized by severity. However, some cases of STGD1 remain unsolved, and disease severity for many variants remains unknown. Increasing our understanding of the genetic pathology of Stargardt disease will drive the development of future therapies.