June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Genotype-phenotype correlation and disease modeling in RPGR-related cone and cone-rod dystrophies.
Author Affiliations & Notes
  • Marco Nassisi
    Institut de la vision, Paris, Île-de-France, France
    Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
  • Giuseppe De Bartolo
    Institut de la vision, Paris, Île-de-France, France
  • Saddek Mohand-Said
    Institut de la vision, Paris, Île-de-France, France
  • Christel Condroyer
    Institut de la vision, Paris, Île-de-France, France
  • Aline Antonio
    Institut de la vision, Paris, Île-de-France, France
  • Marie-Elise Lancelot
    Institut de la vision, Paris, Île-de-France, France
  • Kinga Maria Bujakowska
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Vasily M. SMIRNOV
    Institut de la vision, Paris, Île-de-France, France
  • Thomas Pugliese
    Institut de la vision, Paris, Île-de-France, France
  • John Neidhardt
    Carl von Ossietzky Universitat Oldenburg Fakultat VI Medizin und Gesundheitswissenschaften, Oldenburg, Niedersachsen, Germany
  • Jose Alain Sahel
    Institut de la vision, Paris, Île-de-France, France
  • Christina Zeitz
    Institut de la vision, Paris, Île-de-France, France
  • Isabelle S Audo
    Institut de la vision, Paris, Île-de-France, France
  • Footnotes
    Commercial Relationships   Marco Nassisi None; Giuseppe De Bartolo None; Saddek Mohand-Said None; Christel Condroyer None; Aline Antonio None; Marie-Elise Lancelot None; Kinga Bujakowska None; Vasily SMIRNOV None; Thomas Pugliese None; John Neidhardt None; Jose Sahel None; Christina Zeitz None; Isabelle Audo None
  • Footnotes
    Support  This work was supported by the Foundation Fighting Blindness (clinical fellowship award (MN) [CD-CL-0619-0759-INSERM]). Additional funding: LABEX LIFESENSES [reference ANR-10-LABX-65] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program [ANR-11-IDEX-0004-0]; IHU FOReSIGHT [ANR-18-IAHU-0001] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program; Foundation Fighting Blindness center grant [C-CMM-0907-0428-INSERM04]. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the abstract; and decision to submit the abstract to the ARVO annual meeting 2022.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 138 – A0318. doi:
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      Marco Nassisi, Giuseppe De Bartolo, Saddek Mohand-Said, Christel Condroyer, Aline Antonio, Marie-Elise Lancelot, Kinga Maria Bujakowska, Vasily M. SMIRNOV, Thomas Pugliese, John Neidhardt, Jose Alain Sahel, Christina Zeitz, Isabelle S Audo; Genotype-phenotype correlation and disease modeling in RPGR-related cone and cone-rod dystrophies.. Invest. Ophthalmol. Vis. Sci. 2022;63(7):138 – A0318.

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

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Abstract

Purpose : Variants in the retinitis pigmentosa GTPase regulator gene (RPGR) and, specifically, in its retinal isoform opening reading frame-15 (RPGRORF15) have been associated with rod-cone (RCD), cone and cone-rod dystrophies (CD and CRD). While RPGR-related RCD is well understood, the characteristics and progression of RPGR-related CD/CRD were less frequently investigated. Here, we report the genotyping and genotype-phenotype correlation of a large cohort of patients with RPGR-related CD/CRD.

Methods : 34 index patients and 2 affected relatives were recruited at the “Quinze-Vingts” Hospital, Paris, France. Genetic screening was performed through direct Sanger sequencing of the RPGRORF15. Phenotypic data were collected retrospectively.

Results : 29 distinct variants in RPGRORF15 were identified, of which 27 were frameshift or nonsense and 24 were located towards the 3’ end of the RPGRORF15 transcript. 20 variants are novel sequence alterations. 15 subjects were affected by CD and 19 were diagnosed with CRD. Mean age at last examination was 43,97 ± 11,24 years. Best corrected visual acuity (BCVA) was 0.97 ± 0.71 LogMAR (20/200 Snellen equivalent). The most important predictors of BCVA seem related to morphologic data, with a significant correlation found for the central retinal thickness (β coeff. -0.523, p=0.003), autofluorescence (β coeff. 0.353, p=0.044) and peripapillary sparing (β coeff. -0.376, p=0.031). When analyzing longitudinal data, progressive decline of BCVA was noted, with more than 60% of the patients reaching a BCVA ≥ 1 LogMar in the best eye during their sixth decade of life.

Conclusions : We confirmed that RPGRORF15 variants associated with CD/CRD phenotypes are mostly located within the 3' end of the transcript (C-terminal part of the protein). Several imaging parameters may be useful as prognostic factors in these patients, although prospective longitudinal studies will be needed to confirm these results. The longitudinal data showed a rapidly progressive disease, possibly locating an optimal window of intervention for future therapies in younger ages.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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