Age-related macular degeneration in grandparents of patients with Stargardt disease: Genetic study

PURPOSE: To report clinical features and molecular genetic study in three u nrelated families in which age-related macular degeneration was observed in grandparents of patients with Stargardt disease. METHODS: A complete ophth almologic examination including best-corrected visual acuity measurement, f undus examination, and fluorescein angiography eras per formed on all membe rs of the three families. The entire coding sequence of the ABCR gene was a nalyzed using a combination of single strand conformation polymorphism and direct sequence analysis of the 50 exons, RESULTS: Compound heterozygous mi ssense mutations were observed in patients with Stargardt disease (Arg212Cy s, Arg1107Cys, Gly1977Ser, Arg2107His, and le2113Met). Heterozygous missens e mutations were observed in the grandparents with age-related macular dege neration (Arg212Cys and Arg1107Cys). CONCLUSIONS: We report phenotype and g enotype findings in three unrelated families segregating patients with Star gardt disease and age-related macular degeneration. The hypothesis that the Arg212Cys and Arg1107Cys ABCR gene mutations could be susceptibility facto rs for age-related macular degeneration is discussed. We speculate that the relatives of patients affected with Stargardt disease who are carriers of heterozygous ABCR gene mutations may have a higher risk of developing age-r elated macular degeneration. (C) 1999 by Elsevier Science Inc. All rights r eserved.