EYS is a major gene for rod-cone dystrophies in France

Authors

  • Isabelle Audo,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
    5. Department of Molecular Genetics, Institute of Ophthalmology, London, UK
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  • José-Alain Sahel,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
    5. Department of Molecular Genetics, Institute of Ophthalmology, London, UK
    6. Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
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  • Saddek Mohand-Saïd,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
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  • Marie-Elise Lancelot,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
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  • Aline Antonio,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
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  • Veselina Moskova-Doumanova,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
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  • Emeline F. Nandrot,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
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  • Jordan Doumanov,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
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  • Isabel Barragan,

    1. Unidad Clínica de Genética, Reproducción y Medicina Fetal. Hospital Universitario Virgen del Rocío, Seville, Spain, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Seville, Spain
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  • Guillermo Antinolo,

    1. Unidad Clínica de Genética, Reproducción y Medicina Fetal. Hospital Universitario Virgen del Rocío, Seville, Spain, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Seville, Spain
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  • Shomi S. Bhattacharya,

    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    4. Department of Molecular Genetics, Institute of Ophthalmology, London, UK
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  • Christina Zeitz

    Corresponding author
    1. INSERM, U968, Paris, F-75012, France
    2. CNRS, UMR_7210. Paris, F-75012, France
    3. UPMC Univ Paris 06, UMR_S 968, Department of Genetics, Institut de la Vision, Paris, F-75012, France
    • INSERM, UMR_S968; CNRS, UMR_7210, UPMC Univ Paris 06, Department of Genetics, Institut de la Vision, 17 Rue Moreau, F-75010 Paris, France
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  • Communicated by Nobuyoshi Shimizu

Abstract

Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of 239 sporadic and arRP French cases. Direct sequencing of EYS was performed in 186 subjects for whom known mutations had previously been excluded by applying microarray technology. We mostly identified novel mutations in EYS in a total of 29 patients: Fifteen of the mutations were predicted to create premature stop codons and two represent exonic deletions. In addition, twenty missense, silent or splice-site mutations were detected. Patients revealed homozygous or compound heterozygous mutations and in some cases, only a single mutation. Most patients showed classical signs of RP with relatively preserved central vision and visual field until late in the course of the disorder. One patient showed predominance of the disease in the inferior part of the retina suggesting potential phenotypic variability. With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere. © 2010 Wiley-Liss, Inc.

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