Homozygous c.1937+1G>A splice-site variant of the ABCA4 gene is associated with Stargardt disease.

bstract Purpose: To report the phenotype of homozygous ABCA4 c.1937+1G>A splice-site variant associated with Stargardt disease. Methods: Two siblings, a 10-year-old boy and a 32-year-old woman, born from consanguineous parents, presented with central vision loss and macular pigmentary atrophic changes suggestive of Stargardt disease. After genetic counselling, ABCA4 gene analysis was performed. Results: The 2 siblings affected were shown to be homozygous for the c.1937+1G>A splice junction variant of the ABCA4 gene. Both parents were heterozygous for the same mutation; they were asymptomatic and the fundus examination revealed a normal appearance. Conclusions: Thus far, ABCA4 c.1937+1G>A splice-site variant was shown to cause retinitis pigmentosa when in hemizygosity and Stargardt disease when present on one allele. In this family two sibs homozygous for the ABCA4 c.1937+1G>A splice-site variant have a less severe phenotype of Stargardt disease. This observation provides useful information for the diagnosis and counseling of patients with this ABCA4 variant. © 2014 Wichtig Publishing.