Retinitis Punctata Albescens and RLBP1-Allied Phenotypes

• Published in: Ophthalmology Science
• Main Authors: Bocquet, Béatrice, El Alami Trebki, Hicham, Roux, Anne-Françoise, Labesse, Gilles, Brabet, Philippe, Arndt, Carl, Zanlonghi, Xavier, Defoort-Dhellemmes, Sabine, Hamroun, Dalil, Boulicot-Séguin, Céline, Lequeux, Léopoldine, Picot, Marie Christine, Huguet, Hélèna, Audo, Isabelle, Dhaenens, Claire Marie, Kalatzis, Vasiliki, Meunier, Isabelle
• Other Authors: Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Centre de Biochimie Structurale Montpellier (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital universitaire Robert Debré Reims (CHU Reims), Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou, Service d’Exploration de la Vision et Neuro-ophtalmologie CHU Lille, Hôpital Roger Salengro Lille -Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Hôpital la Colombière CHU Montpellier, Service Génétique Médicale CHU Toulouse, Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie CHU Toulouse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Montpellier (UM), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Sorbonne Université (SU), University College of London London (UCL), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)
• Format: Article in Journal/Newspaper
• Language: English
• Published: CCSD 2021
• Subjects: Bothnia dystrophy; CRALBP; gene therapy; Newfoundland rod–cone dystrophy; retinitis punctata albescens; RLBP1; spectral-domain OCT; variant classification; visual cycle; white dots; [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; Newfoundland
• Online Access: https://hal.science/hal-04929168; https://hal.science/hal-04929168v1/document; https://hal.science/hal-04929168v1/file/1-s2.0-S2666914521000506-main.pdf; https://doi.org/10.1016/j.xops.2021.100052

International audience Purpose: To identify relevant criteria for gene therapy based on clinical and genetic characteristics of rodecone dystrophy associated with RLBP1 pathogenic variants in a large cohort comprising children and adults.Design: Retrospective cohort study.Participants: Patients with pathogenic variants in RLBP1 registered in a single French reference center specialized in inherited retinal dystrophies.Methods: Clinical, multimodal imaging, and genetic findings were reviewed.Main Outcome Measures: Age of onset; visual acuity; ellipsoid line length; nasal, temporal, and foveal retinal thickness; and pathogenic variants and related phenotypes, including Newfoundland rodecone and Bothnia dystrophies (NFRCDs), were reappraised.Results: Twenty-one patients (15 families) were included. The most frequent form was NFRCD with 12 patients (8 families) homozygous for the recurrent deletion of exons 7 through 9 in RLBP1 and 5 patients (4 families) with biallelic protein-truncating variants (2 novel: p.Gln16* and p.Tyr251*). A novel combination of the p.Arg234Trp Bothnia variant with a nonsense variant in trans led to Bothnia dystrophy in 2 sisters. One proband carrying the p.Met266Lys Bothnia variant and in trans p.Arg121Trp and a second, with the p.Arg9Cys and p.Tyr111* combination, both demonstrated mild retinitis punctata albescens. Independently of genotype, all patients showed a visual acuity of worse than 20/200, an ellipsoid line width of less than 1000 mm, and a mean foveal thickness of less than 130 to 150 mm, with loss of both the interdigitation and ellipsoid lines.Conclusions: The eligibility for RLBP1 gene therapy first should be determined according to the biallelic variant combination using a robust classification as proposed herein. An ellipsoid line width of more than 1200 mm and a central thickness of more than 130 to 150 mm with detectable ellipsoid and interdigitation lines should be 2 prerequisite imaging indicators for gene therapy.