1. TRPM1 Is Mutated in Patients with Autosomal-Recessive Complete Congenital Stationary Night Blindness
- Author
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Xavier Guillonneau, Veselina Moskova-Doumanova, Marie-Elise Lancelot, Kinga M. Bujakowska, José-Alain Sahel, Samuel G. Jacobson, Elfride De Baere, Daniel F. Schorderet, Sabine Defoort-Dhellemmes, Christina Zeitz, Agnes B. Renner, Wolfgang Berger, Aline Antonio, Isabelle Audo, Susanne Kohl, Saddek Mohand-Said, Bart P. Leroy, Markus N. Preising, Antje Bernd, Charlotte M. Poloschek, Bernd Wissinger, Eberhart Zrenner, Christian P. Hamel, Ulrich Kellner, Emeline F. Nandrot, Birgit Lorenz, Francis L. Munier, Thierry Léveillard, Isabelle Drumare, Shomi S. Bhattacharya, Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Institute of Ophthalmology [London], University College of London [London] (UCL), Institute for Ophthalmic Research [Tübingen, Germany] (Centre for Ophthalmology), University of Tübingen, Center for Medical Genetics [Ghent], Ghent University Hospital, Universiteit Gent = Ghent University [Belgium] (UGENT), Fondation Asile des aveugles - Hôpital Ophtalmique Jules-Gonin [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), University of Lausanne (UNIL), Justus-Liebig-University [Gießen, Germany], AugenZentrum Siegburg-MVZ ADTC Siegburg GmbH [Germany], University Medical Center of Regensburg [Regensburg, Germany], University Clinics Tuebingen [Germany], University of Freiburg [Freiburg], Neurosciences fonctionnelles et pathologies (NFP), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Éloi [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universität Zürich [Zürich] = University of Zurich (UZH), University of Pennsylvania [Philadelphia], University of Zurich, Zeitz, C, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Université de Lausanne = University of Lausanne (UNIL), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), University of Pennsylvania, and Nandrot, Emeline
- Subjects
Male ,Candidate gene ,Heterozygote ,2716 Genetics (clinical) ,Nonsense mutation ,TRPM Cation Channels ,Genes, Recessive ,610 Medicine & health ,Biology ,medicine.disease_cause ,Nuclear Family ,03 medical and health sciences ,11124 Institute of Medical Molecular Genetics ,0302 clinical medicine ,1311 Genetics ,Night Blindness ,Night vision ,Report ,medicine ,Electroretinography ,Genetics ,Missense mutation ,Humans ,Genetics(clinical) ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Genetics (clinical) ,TRPM1 ,030304 developmental biology ,Congenital stationary night blindness ,0303 health sciences ,Mutation ,medicine.diagnostic_test ,Models, Genetic ,Homozygote ,Pedigree ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,030221 ophthalmology & optometry ,570 Life sciences ,biology ,Female ,sense organs - Abstract
International audience; Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone responses. Although many cases of complete CSNB (cCSNB) are caused by mutations in NYX and GRM6, in~60% of the patients the gene defect remains unknown. Animal models of human diseases are a good source for candidate genes, and we noted that a cCSNB phenotype present in homozygous Appaloosa horses is associated with downregulation of TRPM1. TRPM1, belonging to the family of transient receptor potential channels, is expressed in ON bipolar cells and therefore qualifies as an excellent candidate. Indeed, mutation analysis of 38 patients with CSNB identified ten unrelated cCSNB patients with 14 different mutations in this gene. The mutation spectrum comprises missense, splice-site, deletion, and nonsense mutations. We propose that the cCSNB phenotype in these patients is due to the absence of functional TRPM1 in retinal ON bipolar cells.
- Published
- 2009
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