Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential.
OBJECTIVE
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.


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


METHODS
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.


METHODS
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.
Jacobson
Samuel G
SG
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. jacobsos@mail.med.upenn.edu
Cideciyan
Artur V
AV
Aleman
Tomas S
TS
Sumaroka
Alexander
A
Schwartz
Sharon B
SB
Roman
Alejandro J
AJ
Stone
Edwin M
EM
D000328:Adult; D001766:Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D003598:Cytoskeletal Proteins; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
D003598:Cytoskeletal Proteins; D011506:Proteins; C415903:RPGRIP1 protein, human