title: A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease.
abstract: OBJECTIVE
  To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease.
  
  
  METHODS
  A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene.
  
  
  RESULTS
  We identified a previously unreported kindred of eight siblings, four of whom had mutations in both of their ABCR alleles. A previously described G-to-C transversion of nucleotide 2588, predicting a Gly863Ala amino acid substitution, and a novel G-to-A transition of nucleotide 161, resulting in a Cys54Tyr substitution, were identified. These mutations co-segregated with the affected members of this family. Three of the siblings demonstrated clinical features characteristic of classic Stargardt disease, with bilateral regions of macular atrophy associated with yellow-white "flavimaculatus" flecks in the posterior pole at the level of the retinal pigment epithelium. The fourth affected sibling showed features of early Stargardt disease, with a beaten-bronze appearance to both maculas, as well as perimacular flecks. In all four affected patients, fluorescein angiography showed a characteristic peripheral dark choroid.
  
  
  CONCLUSIONS
  We have identified both a previously described and a novel mutation 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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. zhangk@welchlink.welch.jhu.edu
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: D C
authors.initials: DC
authors.lastname: Garibaldi
authors.forename: M
authors.initials: M
authors.lastname: Kniazeva
authors.forename: T
authors.initials: T
authors.lastname: Albini
authors.forename: M F
authors.initials: MF
authors.lastname: Chiang
authors.forename: M
authors.initials: M
authors.lastname: Kerrigan
authors.forename: J S
authors.initials: JS
authors.lastname: Sunness
authors.forename: M
authors.initials: M
authors.lastname: Han
authors.forename: R
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D014792:Visual Acuity
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters