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Phenotype-Genotype Correlations in Retinal Degenerations Caused by Abcr gene Mutations

  • Jean-Michel Rozet
  • Sylvie Gerber
  • Imad Ghazi
  • Isabelle Perrault
  • Eric Souied
  • Dominique Ducroq
  • Annick Cabot
  • Jean-Louis Dufier
  • Gabriel Coscas
  • Gisèle Soubrane
  • Arnold Munnich
  • Josseline Kaplan

Abstract

Stargardt disease (STGD) and late-onset fundus flavimaculatus (FFM) are autosomal recessive conditions leading to macular degenerations in childhood and adulthood, respectively. Recently, mutations of the photoreceptor cell-specific ATP binding transporter gene (ABCR) have been reported in STGD on one hand, and in some age related macular dystrophies (AMD) on the other hand. In addition, autosomal recessive retinitis pigmentosa (RP19) has recently been ascribed to mutations in the same gene. To provide the first genotype-phenotype correlations in ABCR gene mutations, the screening of the 50 exons encoding ABCR have been performed in a large series of FFM and STGD families as well as in familial cases of AMD and in pedigrees segregating both STGD and RP19. Giving consideration to the results of this study, we suggest that homozygosity for truncating ABCR gene mutations result in severe RP while compound heterozygosity for frameshift and missense mutations at this locus result in a severe macular disorder, STGD. Conversely, all mutations identified in milder macular disorder, FFM, were missense mutations. Finally, some AMD patients were found to carry heterozygote ABCR gene mutations, suggesting that these mutations could represent in some cases a susceptibility factor for the disease.

Keywords

Missense Mutation Retinitis Pigmentosa Retinal Degeneration Splice Mutation Macular Dystrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  • Jean-Michel Rozet
    • 1
  • Sylvie Gerber
    • 1
  • Imad Ghazi
    • 2
  • Isabelle Perrault
    • 1
  • Eric Souied
    • 1
  • Dominique Ducroq
    • 1
  • Annick Cabot
    • 1
  • Jean-Louis Dufier
    • 2
  • Gabriel Coscas
    • 3
  • Gisèle Soubrane
    • 3
  • Arnold Munnich
    • 1
  • Josseline Kaplan
    • 1
  1. 1.Unité de Recherches sur les Handicaps Génétiques de l’Enfant INSERM U-393Hôpital des Enfants Malades, 149 rue de SèvresParis Cedex 15France
  2. 2.Service d’OphthalmologieHôpital NeckerParisFrance
  3. 3.Clinique OphthalmologiqueHôpital Intercommunal de CréteilCréteilFrance

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