September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
MERTK mutations account for 2% of cases with inherited retinal dystrophy in a large French cohort
Author Affiliations & Notes
  • Isabelle S Audo
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
    CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC 1423, 28 rue de Charenton, 75012 Paris, France, Paris, France
  • Elise Boulanger-Semama
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Saddek Mohand-Said
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
    CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC 1423, 28 rue de Charenton, 75012 Paris, France, Paris, France
  • Vanessa Démontant
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Christel Condroyer
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Aline Antonio
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Fiona Boyard
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Said El Shamieh
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Jose Sahel
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
    CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC 1423, 28 rue de Charenton, 75012 Paris, France, Paris, France
  • Christina Zeitz
    Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France, Paris, France
  • Footnotes
    Commercial Relationships   Isabelle Audo, None; Elise Boulanger-Semama, None; Saddek Mohand-Said, None; Vanessa Démontant, None; Christel Condroyer, None; Aline Antonio, None; Fiona Boyard, None; Said El Shamieh, None; Jose Sahel, None; Christina Zeitz, None
  • Footnotes
    Support  Foundation Voir et Entendre, Foundation Fighting Blindness (FFB) [CD-CL-0808- 0466-CHNO] and FFB center, [FFB grantC-GE-0912-0601-INSERM02], Prix de la Fondation de l’OEil, Prix Berthe Fouassier Fondation de France, Ville de Paris and Region Ile de France and by the French State program "Investissements d'Avenir" managed by the Agence Nationale de la Recherche [LIFESENSES: ANR-10-LABX-65]; "Global Care Initiative" grant
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 660. doi:
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      Isabelle S Audo, Elise Boulanger-Semama, Saddek Mohand-Said, Vanessa Démontant, Christel Condroyer, Aline Antonio, Fiona Boyard, Said El Shamieh, Jose Sahel, Christina Zeitz; MERTK mutations account for 2% of cases with inherited retinal dystrophy in a large French cohort. Invest. Ophthalmol. Vis. Sci. 2016;57(12):660.

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

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Abstract

Purpose : MER tyrosine kinase (MERTK) encodes a surface receptor in the retinal pigment epithelium playing a critical role in photoreceptor outer segment internalization prior to phagocystosis. Mutations in this gene have been associated with severe autosomal recessive retinal dystrophies in the RCS rat model and in humans. The purpose of this study was to report genetic findings and phenotypic characteristics of patients affected with retinal dystrophies due to mutations in MERTK in a large cohort of patients applying state of the art techniques.

Methods : A large French cohort of 1004 patients with inherited retinal diseases underwent a full ophthalmic examination. Informed consent was obtained from each patient and unaffected family member. The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local ethics committee. The DNA of patients with a presumed diagnosis of autosomal recessive Rod-Cone Dystrophy and Cone-Rod Dystrophy was assessed. Microarray analysis, targeted Next Generation Sequencing (NGS) and Sanger sequencing were applied to 904 RCD and 100 Cone-Rod Dystrophies. NGS data was also analyzed to detect Copy Number Variation and cases with large deletion were documented applying Multiplex Ligation-dependent Probe Amplification. Familial cosegregation analysis was performed when possible.

Results : A total of 19 patients from 16 unrelated families were found to carry predicted pathogenic mutations in MERTK including 16 cases of RCD and 3 cases of CRD. Sixteen distinct mutations were identified among which 7 are novel. Mutation spectrum in our cohort includes 2 small deletions, 2 small duplications, 1 large exonic deletion, 2 splice-site defects, 6 missense and 3 nonsense changes. The 19 patients carrying these mutations had severe inherited retinal disease with early onset macular involvement.

Conclusions : Our study revealed that mutations in MERTK account for ~2% of inherited retinal dystrophies in France. This new data are useful in the context of current and future therapeutic trials including gene replacement therapy or cell based therapy.

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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