September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Clinical characterization and genotype-phenotype correlations in PDE6A-related retinitis pigmentosa
Author Affiliations & Notes
  • Ditta Zobor
    Institute for Ophthalmic Research, University Tübingen, Germany, Tübingen, Germany
  • Laura Kühlewein
    Institute for Ophthalmic Research, University Tübingen, Germany, Tübingen, Germany
  • Nicole Weisschuh
    Molecular Genetics Laboratory, Institute for Ophthalmic Research, University Tübingen, Tübingen, Germany
  • Christian P Hamel
    Institute of Neurosciences of Montpellier, Hôpital Saint Eloi Montpellier, Montpellier, France
  • Bart Peter Leroy
    Center for Medical Genetics, Department of Ophthalmology, Ghent University Hospital Ghent, Ghent, Belgium
  • Sten Andreasson
    Department of Ophthalmology, Lund University, Lund, Sweden
  • Ayuso Carmen
    Department of Genetics, Instituto de Investigacion Sanitaria-University Hospital Fundacion Jimenez Diaz (IIS - FJD, UAM), Madrid, Spain
  • Günther Rudolph
    Department of Ophthalmology, Ludwig-Maximilians-University Munich, Munich, Germany
  • Bernd Wissinger
    Molecular Genetics Laboratory, Institute for Ophthalmic Research, University Tübingen, Tübingen, Germany
  • Susanne Kohl
    Molecular Genetics Laboratory, Institute for Ophthalmic Research, University Tübingen, Tübingen, Germany
  • Eberhart Zrenner
    Institute for Ophthalmic Research, University Tübingen, Germany, Tübingen, Germany
    Werner Reichardt Centre for Integrative Neuroscience (CIN); University Tübingen, Tübingen, Germany
  • Footnotes
    Commercial Relationships   Ditta Zobor, None; Laura Kühlewein, None; Nicole Weisschuh, None; Christian Hamel, None; Bart Leroy, None; Sten Andreasson, None; Ayuso Carmen, None; Günther Rudolph, None; Bernd Wissinger, None; Susanne Kohl, None; Eberhart Zrenner, None
  • Footnotes
    Support  Tistou & Charlotte Kerstan Stiftung
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 152. doi:
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    • Get Citation

      Ditta Zobor, Laura Kühlewein, Nicole Weisschuh, Christian P Hamel, Bart Peter Leroy, Sten Andreasson, Ayuso Carmen, Günther Rudolph, Bernd Wissinger, Susanne Kohl, Eberhart Zrenner; Clinical characterization and genotype-phenotype correlations in PDE6A-related retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2016;57(12):152.

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

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Abstract

Purpose : Mutations in the PDE6A gene - encoding the a-subunit of the rod cGMP-phosphodiesterase - account for 1% of autosomal recessive retinitis pigmentosa (arRP) through impaired regulation of cGMP levels in the rod outer segment. This study aims for a detailed clinical characterization of patients with PDE6A mutations.

Methods : Data from 28 patients (15 female, 13 male, age: 18 - 83y, mean 39.3±13.3y) with genetically confirmed PDE6A mutations were collected. Besides psychophysical tests (ETDRS visual acuity (VA), kinetic visual field (VF), Roth Hue 28 color vision test, dark adaptation), detailed electrophysiological examination was carried out including Ganzfeld and multifocal ERG (mfERG). Furthermore, fundus autofluorescence and spectral domain OCT imaging were performed for an in-depth morphological characterization.

Results : disease varied considerably. The two siblings homozygous for p.V685M showed markedly reduced visual function (mean VA: 0.9±0.1 logMAR; mean VF for target III4e: 187.5±68 deg2, mean central retinal thickness (CRT): 118.25±16 µm) and no recordable ERG responses. In comparison, most patients revealed significantly better visual function (mean VA: 0.35±0.36 logMAR ; mean VF: 3061.94±3643.2 deg2, mean CRT: 202.95±83.22 µm). Although Ganzfeld ERGs were mostly non-recordable, mfERGs showed residual responses in these cases. Significant heterogeneity was observed in the rate of progression over age, in some cases with a remarkably slow time course. The two siblings homozygous for p.R102S presented with well-preserved function (mean VA: 0.0±0 logMAR, mean VF: 12304.8±854.8 deg2, mean CRT: 216.75±7.58 µm) and remaining ERG responses. For all patients, a high degree of left to right eye symmetry was found with a higher correlation efficient for CRT (r=0.87) than for VA (r=0.71).

Conclusions : Mutations in the PDE6A gene cause typical arRP, but with highly heterogenous disease courses depending on the genotype. The p.V685M mutation seemed to cause worse clinical outcome - especially if patients were homozygous for this mutation, while the p.R102S mutation was linked to milder diseases manifestation. These findings will be useful for the identification of patients concerning future therapeutic trials. The observed good intra-individual symmetry is highly relevant for any interventional trial as the second eye will be able to serve as an internal control.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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