PHENOTYPIC CHARACTERISTICS OF ROD–CONE DYSTROPHY ASSOCIATED WITH MYO7A MUTATIONS IN A LARGE FRENCH COHORT

Samer Khateb (1, 2, 3) , Saddek Mohand-Saïd (4, 3) , Marco Nassisi (2, 3) , Crystel Bonnet (5, 2) , Anne-Françoise Roux (6) , Camille Andrieu (3) , Aline Antonio (2, 3) , Christel Condroyer (2) , Christina Zeitz (2) , Céline Devisme (3) , Natalie Loundon (7, 8) , Sandrine Marlin (8) , Christine Petit (2, 5, 9) , Bahram Bodaghi (10) , José-Alain Sahel (2, 3, 11, 12, 13) , Isabelle Audo (2, 3, 14)

1 HUJ - The Hebrew University of Jerusalem
2 Institut de la Vision
3 CHNO - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
4 Institut de la Vision
5 Génétique et Physiologie de l'Audition
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
7 CHU Necker - Enfants Malades [AP-HP]
8 Centre de référence des Surdités Génétiques [CHU Necker, Paris]
9 Collège de France - Chaire Génétique et physiologie cellulaire
10 CHU Pitié-Salpêtrière [AP-HP]
11 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
12 University of Pittsburgh School of Medicine
13 Académie des Sciences [Paris]
14 UCL - University College of London [London]

Purpose: To document the rod-cone dystrophy phenotype of patients with Usher syndrome type 1 (USH1) harboring MYO7A mutations. Methods: Retrospective cohort study of 53 patients (42 families) with biallelic MYO7A mutations who underwent comprehensive examination, including functional visual tests and multimodal retinal imaging. Genetic analysis was performed either using a multiplex amplicon panel or through direct sequencing. Data were analyzed with IBM SPSS Statistics software v. 21.0. Results: Fifty different genetic variations including 4 novel were identified. Most patients showed a typical rod-cone dystrophy phenotype, with best-corrected visual acuity and central visual field deteriorating linearly with age. At age 29, binocular visual field demonstrated an average preservation of 50 central degrees, constricting by 50% within 5 years. Structural changes based on spectral domain optical coherence tomography, short wavelength autofluorescence, and near-infrared autofluorescence measurements did not however correlate with age. Our study revealed a higher percentage of epiretinal membranes and cystoid macular edema in patients with MYO7A mutations compared with rod-cone dystrophy patients with other mutations. Subgroup analyses did not reveal substantial genotype-phenotype correlations. Conclusion: To the best of our knowledge, this is the largest French cohort of patients with MYO7A mutations reported to date. Functional visual characteristics of this subset of patients followed a linear decline as in other typical rod-cone dystrophy, but structural changes were variable indicating the need for a case-by-case evaluation for prognostic prediction and choice of potential therapies.

Domains: Life Sciences [q-bio]

Samer Khateb, Saddek Mohand-Saïd, Marco Nassisi, Crystel Bonnet, Anne-Françoise Roux, et al.. PHENOTYPIC CHARACTERISTICS OF ROD–CONE DYSTROPHY ASSOCIATED WITH MYO7A MUTATIONS IN A LARGE FRENCH COHORT. RETINA. The Journal of Retinal and Vitreous Diseases, 2020, 40 (8), pp.1603-1615. ⟨10.1097/IAE.0000000000002636⟩. ⟨pasteur-03215234⟩