1. Loss of Function of RIMS2 Causes a Syndromic Congenital Cone-Rod Synaptic Disease with Neurodevelopmental and Pancreatic Involvement.
- Author
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Mechaussier S, Almoallem B, Zeitz C, Van Schil K, Jeddawi L, Van Dorpe J, Dueñas Rey A, Condroyer C, Pelle O, Polak M, Boddaert N, Bahi-Buisson N, Cavallin M, Bacquet JL, Mouallem-Bézière A, Zambrowski O, Sahel JA, Audo I, Kaplan J, Rozet JM, De Baere E, and Perrault I
- Subjects
- Adult, Alleles, Alternative Splicing, Brain metabolism, Cell Line, Child, Child, Preschool, Diagnosis, Differential, Family Health, Female, France, GTP-Binding Proteins chemistry, GTP-Binding Proteins metabolism, Glucose metabolism, Humans, Insulin Secretion, Male, Nerve Tissue Proteins chemistry, Nerve Tissue Proteins metabolism, Pancreas metabolism, Pedigree, Retina metabolism, Saudi Arabia, Senegal, Eye Diseases, Hereditary genetics, GTP-Binding Proteins genetics, Genetic Diseases, X-Linked genetics, Loss of Function Mutation, Myopia genetics, Nerve Tissue Proteins genetics, Night Blindness genetics
- Abstract
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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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