title: Age-related macular degeneration in grandparents of patients with Stargardt disease: genetic study.
abstract: OBJECTIVE
  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, Argl107Cys, 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.
authors.affiliation: Clinique Ophtamologique Universitaire de Créteil, France.
authors.forename: E H
authors.initials: EH
authors.lastname: Souied
authors.forename: D
authors.initials: D
authors.lastname: Ducroq
authors.forename: S
authors.initials: S
authors.lastname: Gerber
authors.forename: I
authors.initials: I
authors.lastname: Ghazi
authors.forename: J M
authors.initials: JM
authors.lastname: Rozet
authors.forename: I
authors.initials: I
authors.lastname: Perrault
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J L
authors.initials: JL
authors.lastname: Dufier
authors.forename: G
authors.initials: G
authors.lastname: Coscas
authors.forename: G
authors.initials: G
authors.lastname: Soubrane
authors.forename: J
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D012374:Rod Cell Outer Segment / Q000378:metabolism / Q000473:pathology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004247:DNA