May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Human Phenotypes of Rhodopsin Mutations Resulting in Retinal Binding Failure
Author Affiliations & Notes
  • H. Perry Friedman
    Ophthalmology, Columbia University, New York, New York
  • C.-S. Lin
    Ophthalmology, Columbia University, New York, New York
  • S. H. Tsang
    Ophthalmology, Columbia University, New York, New York
  • Footnotes
    Commercial Relationships H. Perry Friedman, None; C. Lin, None; S.H. Tsang, None.
  • Footnotes
    Support Burroughs-Wellcome Fund, FFB, American Geriatrics Society, Hirschl Trust, AUPO-RPB, and NIH-EY004081 HIGHWIRE EXLINK_ID="48:5:3674:1" VALUE="EY004081" TYPEGUESS="GEN" /HIGHWIRE .
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3674. doi:
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    • Get Citation

      H. Perry Friedman, C.-S. Lin, S. H. Tsang; Human Phenotypes of Rhodopsin Mutations Resulting in Retinal Binding Failure. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3674.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: To describe phenotypic manifestations of D190N mutation in rhodopsin gene [RHO, D190N] in two asymptomatic boys. D190N destabilizes retinal Schiff base in dark-state rhodopsin but does not affect the MII activation energy barrier to hydrolysis.

Methods:: A 7- and 11- year old boy with D190N mutant in the rhodopsin gene underwent pattern and full-field electroretinography (PERG, ERG) and fundus autofluorescence (AF) imaging studies were performed. At the highest stimulus intensities, the leading edge of the a-wave is fitted with a computational model based on photopigment transduction to obtain values for the maximum response RmP3 and sensitivity S. Each subject's genomic DNA was extracted from blood and was amplified for sequencing in 50 ul polymerase chain reaction (PCR) reactions using standard methodology.

Results:: D190N mutation was confirmed in these two young boys. Neither patient showed typical vascular attenuation, nor "bone spicule" pigmentation in the midperipheral, nor waxy pallor of the optic disc. Normal funduscoptic examination was seen in the 7-year old. Rare intraretinal pigment migration in both fundi were found in the 11-year old. Pattern ERG suggested normal macular and optic nerve function. Full field electroretinogram showed rod specific b-waves with broadened peaks. The 30 Hz flicker ERG had a mild delay of 1 millisecond compared to controls. Fundus AF of the macula revealed hyperfluorescence rings in the maculae.

Conclusions:: ERG implicit time delay and abnormal macular autofluorescence were early manifestations of retinitis pigmentosa associated with D190N mutation in the rhodopsin gene. Full-field ERG abnormalities indicated characteristic generalized retinal dysfunction and delay in photoreceptor signaling. Autofluorescence (AF) studies suggested that the RPE was involved in early stages of the defects associated with this rod-specific gene. The AF emission spectrum closely resembled that of lipofuscin, a byproduct of outer segment shedding. High density AF lesions suggested localized accumulation of lipofuscin and disruption of RPE metabolism that was associated with photoreceptor death even at an early stage of pathogenesis in the [RHO, D190N] mutation.

Keywords: retinal degenerations: cell biology • gene/expression • signal transduction 

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