Loss of Function of RIMS2 Causes a Syndromic Congenital Cone-Rod Synaptic Disease with Neurodevelopmental and Pancreatic Involvement
| Autor: | Nadia Bahi-Buisson, Christel Condroyer, Isabelle Perrault, Alexandra Mouallem-Beziere, Olivier Pelle, José-Alain Sahel, Josseline Kaplan, Laila Jeddawi, Isabelle Audo, Michel Polak, Jean-Louis Bacquet, Christina Zeitz, Nathalie Boddaert, Olivia Zambrowski, Basamat Almoallem, Jean-Michel Rozet, Jo Van Dorpe, Kristof Van Schil, Sabrina Mechaussier, Mara Cavallin, Alfredo Dueñas Rey, Elfride De Baere |
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| Přispěvatelé: | Université Paris Cité (UPC), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Embryology and genetics of human malformation (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pathology Photophobia [SDV]Life Sciences [q-bio] syndromic Ribbon synapse RIM2-ALPHA chemistry.chemical_compound 0302 clinical medicine Loss of Function Mutation Night Blindness Insulin Secretion differential diagnosis Myopia Medicine and Health Sciences RIMS2 Child Genetics (clinical) AMAUROSIS synaptic membrane exocytosis gene Brain Eye Diseases Hereditary Genetic Diseases X-Linked STATIONARY NIGHT BLINDNESS DYSTROPHY Senegal Pedigree 3. Good health neurodevelopmental or pancreatic involvement medicine.anatomical_structure Child Preschool Female France medicine.symptom Adult EXPRESSION medicine.medical_specialty PROTEINS Saudi Arabia RIBBON SYNAPSES Outer plexiform layer Nerve Tissue Proteins Biology Retina Article Cell Line Diagnosis Differential 03 medical and health sciences GTP-Binding Proteins medicine Genetics Humans congenital cone-rod synaptic disorder Pancreas Alleles Loss function Family Health MUTATIONS Pancreatic islets RIM1-ALPHA Correction Dystrophy Biology and Life Sciences Retinal GENE Alternative Splicing Glucose 030104 developmental biology stationary versus degenerative retinal disease chemistry 030221 ophthalmology & optometry CRSD exome sequencing Immunostaining 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Human Genetics American Journal of Human Genetics, Elsevier (Cell Press), 2020, 106, pp.859-871. ⟨10.1016/j.ajhg.2020.04.018⟩ AMERICAN JOURNAL OF HUMAN GENETICS The American Journal of Human Genetics |
| ISSN: | 0002-9297 1537-6605 |
| DOI: | 10.1016/j.ajhg.2020.04.018⟩ |
| Popis: | Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD. |
| Databáze: | OpenAIRE |
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