Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential

Ophthalmology. 2007 May;114(5):895-8. doi: 10.1016/j.ophtha.2006.10.028. Epub 2007 Feb 16.


Purpose: To determine the treatment potential in Leber congenital amaurosis (LCA) resulting from an RPGRIP1 (retinitis pigmentosa GTPase regulating-interacting protein 1) mutation, a form of LCA with recent gene therapy success in an animal model.

Design: Case report of a rare genetic eye disease investigated for intervention potential.

Participants: A 19-year-old man with LCA.

Methods: We studied the retinal structure and function in an LCA patient with a novel homozygous Val1211Glu mutation in the RPGRIP1 gene using optical coherence tomography and colocalized dark-adapted thresholds.

Main outcome measure: Optical coherence tomography results.

Results: Central retinal laminar architecture was preserved, and there was a measurable outer nuclear layer. The retained retinal structure corresponded to the region of visual sensitivity. With increasing eccentricity, there was no measurable visual function, and retinal laminar disorganization suggested a remodeling process.

Conclusions: The RPGRIP1-LCA patient has treatment potential for a gene replacement strategy if targeted to central, but not pericentral or peripheral, retina. The results differ from similarly studied RPE65-LCA and CRB1-LCA patients. Preclinical progress toward therapy in LCA patients warrants detailed structure-function studies in humans to determine feasibility and candidacy for clinical trials.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blindness / congenital
  • Blindness / diagnosis
  • Blindness / genetics*
  • Cytoskeletal Proteins
  • Genetic Therapy
  • Humans
  • Male
  • Mutation*
  • Proteins / genetics*
  • Retina / pathology
  • Tomography, Optical Coherence
  • Visual Acuity


  • Cytoskeletal Proteins
  • Proteins
  • RPGRIP1 protein, human