A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease

PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Starg ardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evalua tion and fluorescein angiography, Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gen e were analyzed by single stranded confirmation polymorphism analysis, foll owed by direct sequencing of observed variants, to identify mutations in th e ABCR gene. RESULTS: We identified a previously unreported kindred of eight siblings, f our of whom had mutations in both of their ABCR alleles, A previously descr ibed G-to-C transversion of nucleotide 2588, predicting a Gly863Ala amino a cid substitution, and a novel G-to A transition of nucleotide 161, resultin g in a Cys54Tyr substitution, were identified, These mutations co-segregate d with the affected members of this family. Three of the siblings demonstra ted clinical features characteristic of classic Stargardt disease, with bil ateral regions of macular atrophy associated with yellow white "flavimacula tus" flecks in the posterior pole at the level of the retinal pigment epith elium. The fourth affected sibling showed features of early Stargardt disea se, with a beaten-bronze appearance to both maculas, as well as perimacular flecks. In all four affected patients, fluorescein angiography showed a ch aracteristic peripheral dark choroid, CONCLUSIONS: We have identified both a previously described and a novel mut ation in the ABCR gene in four patients with autosomal recessive Stargardt disease. In depth knowledge of the ABCR mutation spectrum in patients with Stargardt disease will provide for more efficient screening and may provide potential therapies for Stargardt disease and other retinal diseases. (C) 1999 by Elsevier Science Inc, All rights reserved.