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, C, Huguet, Hélèna, Audo, Isabelle, Dhaenens, Claire-Marie, Kalatzis, Vasiliki, Meunier, Isabelle
• Other Authors: Centre de référence des affections sensorielles d'origine génétique, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Hôpital Gui de Chauliac CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Clinique Jules Verne, 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, Université de Montpellier (UM), Centre Hospitalier Henri Duffaut (Avignon), Clinique rive gauche, CIC Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Hôpital Saint Eloi CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 d'investigation clinique Quinze-Vingts CHNO (CIC1423 - CIC QUINZE-VINGTS), Institut Hospitalo-Universitaire FOReSIGHT (IHU FOReSIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Sorbonne Université (SU)-Sorbonne Université (SU), 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.