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Different Mutations in RPE65 Are Associated with Variability in the Severity of Retinal Dystrophy

  • Christian P. Hamel
  • Françoise Marlhens
  • Jean-Michel Griffoin
  • Corinne Bareil
  • Mireille Claustres
  • Bernard Arnaud

Abstract

RPE65 encodes a retinal pigment epithelium (RPE)-specific protein thought to be involved in the 11 -cis retinoid metabolism, a key process in vision.To evaluate the visual implications of defects in this gene, we screened patients with various types of inherited retinal dystrophies. We found two nonsense mutations, 1121delA and R234X, in two sibs with Leber’s congenital amaurosis. The presence of either one of the two mutations on each allele indicates that they were compound heterozygotes. In a subsequent screening, two missense mutations, L22P and H68Y, were found in a patient with autosomal recessive retinitis pigmentosa.This individual was also a compound heterozygote. These results suggest that the level of impairment of the RPE65 protein, presumably abnormal activity in the case of amino acid substitutions and absence of protein in the case of null mutations, controls the rate at which the photoreceptors degenerate, and hence the severity of the phenotype.

Keywords

Retinal Pigment Epithelium Amino Acid Substitution Retinitis Pigmentosa Compound Heterozygote Patient III2 
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

  • Christian P. Hamel
    • 1
    • 3
  • Françoise Marlhens
    • 1
  • Jean-Michel Griffoin
    • 1
  • Corinne Bareil
    • 2
  • Mireille Claustres
    • 2
  • Bernard Arnaud
    • 3
  1. 1.Laboratoire de Neurobiologie de l’Audition-Plasticité SynaptiqueINSERM U.254Montpellier cedex 5France
  2. 2.Laboratoire de Biochimie GénétiqueInstitut de BiologieMontpellierFrance
  3. 3.Service d’OphtalmologieHôpital Gui de ChauliacMontpellier cedex 5France

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