July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
CPH1, a new gene for Dominant Optic Atrophy
Author Affiliations & Notes
  • Cecile Delettre Cribaillet
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Camille Mégy
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Xavier Zanlonghi
    Clinique Jules Verne, Nantes, France
  • Isabelle Anne Meunier
    Centre of Reference for Genetic Sensory Diseases, CHU, Montpellier, France
    INSERM U1051, Montpellier, France
  • Marie O Pequignot
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Mélanie Quiles
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Christian Hamel
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Agathe Roubertie
    Centre of Reference for Genetic Sensory Diseases, CHU, Montpellier, France
    INSERM U1051, Montpellier, France
  • Nicole Weisschuh
    Centre for Ophthalmology, Germany
  • Béatrice Bocquet
    Centre of Reference for Genetic Sensory Diseases, CHU, Montpellier, France
    INSERM U1051, Montpellier, France
  • Guy Lenaers
    Institut MitoVasc, France
    Université d'Angers, France
  • Gael Manes
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Bernd Wissinger
    Centre for Ophthalmology, Germany
  • Maria Solà Vilarrubias
    Molecular Biology Institute Barcelona, Spain
  • Hans Spelbrink
    Radboud Center for Mitochondrial Medicine, Netherlands
  • Emmanuelle Sarzi
    INSERM U1051, Montpellier, France
    University of Montpellier, France
  • Footnotes
    Commercial Relationships   Cecile Delettre Cribaillet, None; Camille Mégy, None; Xavier Zanlonghi, None; Isabelle Meunier, None; Marie Pequignot, None; Mélanie Quiles, None; Christian Hamel, None; Agathe Roubertie, None; Nicole Weisschuh, None; Béatrice Bocquet, None; Guy Lenaers, None; Gael Manes, None; Bernd Wissinger, None; Maria Solà Vilarrubias, None; Hans Spelbrink, None; Emmanuelle Sarzi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2811. doi:
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      Cecile Delettre Cribaillet, Camille Mégy, Xavier Zanlonghi, Isabelle Anne Meunier, Marie O Pequignot, Mélanie Quiles, Christian Hamel, Agathe Roubertie, Nicole Weisschuh, Béatrice Bocquet, Guy Lenaers, Gael Manes, Bernd Wissinger, Maria Solà Vilarrubias, Hans Spelbrink, Emmanuelle Sarzi; CPH1, a new gene for Dominant Optic Atrophy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2811.

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

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Abstract

Purpose : Hereditary Optic Neuropathies (HON) are genetically heterogeneous diseases. HON can be isolated, affecting exclusively the retinal ganglion cell, or syndromic. HON are linked to genes coding proteins with a major role in the mitochondrial function. Our purpose is to characterize a new gene causing HON, called CPH1.

Methods : Whole-exome sequencing (WES) method was used to characterize the genetic cause of a new form of Dominant Optic Atrophy associated with a maculopathy. Sanger sequencing was used to verify the mutations. Then, we used fibroblasts to characterize mitochondrial dysfunction in patient cells. Zebrafish model were used to in vivo study effect of the mutation on visual function.

Results : WES analysis was performed on several members of a very large family with a dominant optic atrophy (DOA) and a photoreceptor anomaly in the central part of the retina. A dominant mutation was identified in a candidate gene called CPH1. This gene encodes a protein involved in the mitochondrial function. We then screened CPH1 in a large cohort of DOA families and found additional mutations. Our results on patients’ fibroblasts show that CPH1 protein expression is decreased compared to controls, whereas the mRNA level of CPH1 remained unchanged. Interestingly, fibroblasts carrying the mutation show a decrease of mitochondrial respiratory chain and affection in mitochondria with transmission electron microscopy. We used morpholinos and CPH1 RNA mutant to model the disease in zebrafish. First results show defect in eye development in mutant fish.

Conclusions : These results suggest that CPH1 is a novel gene associated with dominant optic atrophy. Mechanistic study indicated that the mutation in this gene involves severe mitochondrial dysfunction.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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