title: The ABCR gene in recessive and dominant Stargardt diseases: a genetic pathway in macular degeneration.
abstract: Stargardt disease (STGD) is a juvenile-onset macular dystrophy and can be inherited in an autosomal recessive or in an autosomal dominant manner. Genes involved in dominant STDG have been mapped to human chromosomes 13q (STGD2) and 6q (STGD3). Here, we identify a new kindred with dominant STGD and demonstrate genetic linkage to the STGD3 locus. Because of a more severe macular degeneration phenotype of one of the patients in this family, the gene responsible for the recessive STGD1, ABCR, was analyzed for sequence variants in all family members. One allele of the ABCR gene was shown to carry a stop codon-generating mutation (R152X) in three family members, including the one patient who had inherited also the dominant gene. A grandparent of that patient with the same ABCR mutation developed age-related macular degeneration (AMD), consistent with our earlier observation that some variants in the ABCR gene may increase susceptibility to AMD in the heterozygous state. Based on these results, we propose that there is a common genetic pathway in macular degeneration that includes genes for both recessive and dominant STGD.
authors.affiliation: Wilmer Eye Institute, John Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Kniazeva
authors.forename: A
authors.initials: A
authors.lastname: Hutchinson
authors.forename: M
authors.initials: M
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Dean
authors.forename: R
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters