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

• Published in: American journal of ophthalmology 1999-08, Vol.128 (2), p.173-178
• Main Authors: Souied, Eric H, Ducroq, Dominique, Gerber, Sylvie, Ghazi, Imad, Rozet, Jean-Michel, Perrault, Isabelle, Munnich, Arnold, Dufier, Jean Louis, Coscas, Gabriel, Soubrane, Gisèle, Kaplan, Josseline
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Base Sequence; Biological and medical sciences; Child; DNA - analysis; Electrophoresis, Polyacrylamide Gel; Fluorescein Angiography; Fundus Oculi; Genotype; Humans; Macular Degeneration - diagnosis; Macular Degeneration - genetics; Macular Degeneration - metabolism; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation, Missense; Ophthalmology; Pedigree; Phenotype; Polymorphism, Single-Stranded Conformational; Retinopathies; Rod Cell Outer Segment - metabolism; Rod Cell Outer Segment - pathology
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/S0002-9394(99)00145-2

PURPOSE: To report clinical features and molecular genetic study in three unrelated families in which age-related macular degeneration was observed in grandparents of patients with Stargardt disease. METHODS: A complete ophthalmologic examination including best-corrected visual acuity measurement, fundus examination, and fluorescein angiography was performed on all members of the three families. The entire coding sequence of the ABCR gene was analyzed using a combination of single strand conformation polymorphism and direct sequence analysis of the 50 exons. RESULTS: Compound heterozygous missense mutations were observed in patients with Stargardt disease (Arg212Cys, Arg1107Cys, Gly1977Ser, Arg2107His, and le2113Met). Heterozygous missense mutations were observed in the grandparents with age-related macular degeneration (Arg212Cys and Arg1107Cys). CONCLUSIONS: We report phenotype and genotype findings in three unrelated families segregating patients with Stargardt disease and age-related macular degeneration. The hypothesis that the Arg212Cys and Arg1107Cys ABCR gene mutations could be susceptibility factors 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-related macular degeneration.