RP1 and autosomal dominant rod–cone dystrophy: Novel mutations, a review of published variants, and genotype–phenotype correlation

Authors

  • Isabelle Audo,

    Corresponding author
    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
    5. UCL-Institute of Ophthalmology, Bath Street, London, United Kingdom
    • Institut de la Vision, Department of Genetics 17, Rue Moreau, 75012 Paris, France
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  • Saddek Mohand-Saïd,

    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, 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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  • Claire-Marie Dhaenens,

    1. Centre Hospitalier Régional Universitaire de Lille, UF Génopathies, Laboratoire de Biochimie et Biologie Moléculaire- Université Lille Nord de France, Lille, France
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  • Aurore Germain,

    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, Paris, F-75012, France
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  • Elise Orhan,

    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, Paris, F-75012, France
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  • Aline Antonio,

    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, 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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  • Christian Hamel,

    1. Centre de Référence Maladies Sensorielles Génétiques, Hôpital Guy de Chauliac, Montpelier, France
    2. U583, INSERM, Institute for Neurosciences de Montpellier, Montpellier, France
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  • José-Alain Sahel,

    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, Paris, F-75012, France
    4. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, F-75012, France
    5. UCL-Institute of Ophthalmology, Bath Street, London, United Kingdom
    6. Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
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  • Shomi S. Bhattacharya,

    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, Paris, F-75012, France
    4. UCL-Institute of Ophthalmology, Bath Street, London, United Kingdom
    5. Department of Celular Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Isla Cartuja, Seville, Spain
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  • Christina Zeitz

    Corresponding author
    1. INSERM, UMRS968, Paris, F-75012, France
    2. UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
    3. CNRS, UMR_7210, Paris, F-75012, France
    • Institut de la Vision, Department of Genetics 17, Rue Moreau, 75012 Paris, France
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  • Communicated by Peter Humphries

Abstract

Rod–cone dystrophies (retinitis pigmentosa [RP]) are a clinically and genetically heterogeneous group of inherited retinal disorders characterized by photoreceptor degeneration. RP1 is a major gene underlying autosomal dominant (ad) RP, though prevalence figures vary depending on the origin of the cases from 0–10% of all adRP. Some mutations in RP1 also lead to autosomal recessive (ar) RP. Herein, we review all previously reported and several novel RP1 mutations in relation to the associated phenotype in RP1 patients from a French adRP cohort. Prevalence studies from this cohort show that 5.3% of the cases have RP1 mutations. This is in accordance with other studies reported from United Kingdom and United States. The majority of mutations represent truncating mutations that are located in a hot spot region of the gene. Similarly, we identified in total four novel deletions and nonsense mutations, of which two may represent recurrent mutations in this population. In addition, a novel missense mutation of uncertain pathogenicity was identified. Including our findings to date, 47 RP1 mutations are known to cause adRP. Variable penetrance of the disease was observed in our and other cohorts. Most patients with RP1 mutations show classical signs of RP with relatively preserved central vision and visual field. Hum Mutat 33:73–80, 2012. © 2011 Wiley Periodicals, Inc.

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