Contributors: 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); Institut de l'Audition Paris (IDA); Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Genopole Research; Fondation Ophtalmologique Adolphe de Rothschild Paris; Maladies génétiques d'expression pédiatrique (U933); Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau APHP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); CHU Trousseau APHP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Académie des sciences; Department of Ophthalmology Pittsburgh, PA, États-Unis; University of Pittsburgh School of Medicine Pittsburgh, PA, États-Unis; University of Pittsburgh Medical Center Pittsburgh, PA, États-Unis (UPMC)-University of Pittsburgh Medical Center Pittsburgh, PA, États-Unis (UPMC); Institute of Ophthalmology London; University College of London London (UCL); This research was funded by Fondation Voir et Entendre (CZ), Prix Dalloz for “La recherche en ophtalmologie” (CZ), LABEX LIFESENSES (reference ANR-10-LABX-65) supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d’Avenir program (ANR-11-IDEX-0004-0), IHU FOReSIGHT (ANR-18-IAHU-0001) supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d’Avenir program, Foundation Fighting Blindness center grant C-CMM-0907-0428-INSERM04 , grant (BR-GE-0619-0761-INSERM) Prix de la Fondation de l’Œil (IA), UNADEV (Union Nationale des Aveugles et Déficients Visuels) in partnership with ITMO NNP/AVIESAN (alliance nationale pour les sciences de la vie et de la santé) for research in visual disorders, and doctoral funding from the Ministère de l’Enseignement Supérieur et de la Recherche (MESR) and Fondation de France (CM).; ANR-10-LABX-0065,LIFESENSES,DES SENS POUR TOUTE LA VIE(2010); ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011); ANR-18-IAHU-0001,FOReSIGHT,Enabling Vision Restoration(2018)
نبذة مختصرة : International audience ; The purpose of this work was to identify the gene defect underlying a relatively mild rod-cone dystrophy (RCD), lacking disease-causing variants in known genes implicated in inherited retinal disorders (IRD), and provide transcriptomic and immunolocalization data to highlight the best candidate. The DNA of the female patient originating from a consanguineous family revealed no large duplication or deletion, but several large homozygous regions. In one of these, a homozygous frameshift variant, c.244_246delins17 p.(Trp82Valfs*4); predicted to lead to a nonfunctional protein, was identified in CCDC51. CCDC51 encodes the mitochondrial coiled-coil domain containing 51 protein, also called MITOK. MITOK ablation causes mitochondrial dysfunction. Here we show for the first time that CCDC51/MITOK localizes in the retina and more specifically in the inner segments of the photoreceptors, well known to contain mitochondria. Mitochondrial proteins have previously been implicated in IRD, although usually in association with syndromic disease, unlike our present case. Together, our findings add another ultra-rare mutation implicated in non-syndromic IRD, whose pathogenic mechanism in the retina needs to be further elucidated.
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