The phenotypic spectrum of CEP250 gene variants
Year: 2024
Type: article
Study design: Case Report
Abstract: Introduction Classically, Usher syndrome is characterized by the association of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP) and possible vestibular dysfunction. Pathogenic bi-allelic variants in CEP250 cause atypical autosomal recessive Usher syndrome, which is associated with SNHL and photoreceptors dysfunction without vestibular signs. To date, only 19 scattered descriptions have been reported. In this study, we present detailed clinical and genetic description of 7 unrelated individuals with CEP250 related disease, along with a literature review to provide new insight on the severity and course of the disease.Methods We retrospectively recruited 7 unrelated individuals who underwent genetic testing (targeted gene panel or whole genome sequencing) and were found to carry CEP250 pathogenic variants.Results Most patients (5/7) exhibit both retinal dystrophy and SNHL. Two patients appear to present either isolated hearing loss or visual impairment, but further investigations are needed to confirm a possible non-syndromic presentation. All patients harbored isolated truncating variants.Discussion CEP250 pathogenic variants are associated with post-lingual SNHL, and most often progressive photoreceptor dysfunction. The disease may begin with ocular features or hearing loss. We strongly recommend genetic analysis of classical and atypical Usher related-genes, in patients with isolated retinal dystrophy or SNHL. We also recommend ophthalmological evaluation and follow-up in patients with isolated SNHL, and conversely. The coexistence of loss- and gain-of-function effects may exist, complicating the development of gene therapy.
Source: Ophthalmic Genetics
Authors: Cécile Courdier, Claire-Marie Dhaenens, Olivier Grunewald, Anne-Marie Guerrot, Isabelle Audo, Amélie Lecleire-Collet, Isabelle Amstutz-Montadert, Shai Gad, Gabrielle Lapeyre, Xavier Zanlonghi, Dominique Bonneau, Mélanie Fradin, Guylène Le Meur, Sandrine Marlin, Pierre Blanc, Anne-Françoise Roux, Isabelle Meunier, Vincent Michaud
Institutions: Centre Hospitalier Universitaire de Bordeaux, Centre Hospitalier Universitaire de Lille, Lille Neurosciences & Cognition, Centre Hospitalier Universitaire de Rouen, Centre hospitalier national d'ophtalmologie des Quinze-Vingts, Hôpital Charles-Nicolle, Centre Hospitalier Universitaire de Rennes, Centre National de la Recherche Scientifique, Inserm, Centre Hospitalier Universitaire d'Angers, Mitochondrial and Cardiovascular Physiopathology, Université d'Angers, Centre Hospitalier Universitaire de Nantes, Translational Research in Gene Therapy, Nantes Université, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, Institut des Maladies Génétiques Imagine, Université de Montpellier, Centre Hospitalier Universitaire de Montpellier, Institute for Neurosciences of Montpellier, Université de Bordeaux, Maladies Rares: Génétique et Métabolisme
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4404869614