title: Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.
abstract: OBJECTIVE
  To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD).
  
  
  METHODS
  One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified.
  
  
  RESULTS
  The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes.
  
  
  CONCLUSIONS
  This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.
authors.affiliation: Ocular Molecular Genetics Institute, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Briggs
authors.forename: D
authors.initials: D
authors.lastname: Rucinski
authors.forename: P J
authors.initials: PJ
authors.lastname: Rosenfeld
authors.forename: T
authors.initials: T
authors.lastname: Hirose
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters