Poulter, JA, Gravett, MSC orcid.org/0000-0001-8351-7176, Taylor, RL et al. (26 more authors) (2021) New variants and in silico analyses in GRK1 associated Oguchi disease. Human Mutation, 42 (2). humu.24140. pp. 164-176. ISSN 1059-7794
Abstract
Biallelic mutations in G‐Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB). The purpose of this study was to identify disease causing GRK1 variants and use in‐depth bioinformatic analyses to evaluate how their impact on protein structure could lead to pathogenicity. Patients’ genomic DNA was sequenced by whole genome, whole exome or focused exome sequencing. Disease associated variants, published and novel, were compared to nondisease associated missense variants. The impact of GRK1 missense variants at the protein level were then predicted using a series of computational tools. We identified twelve previously unpublished cases with biallelic disease associated GRK1 variants, including eight novel variants, and reviewed all GRK1 disease associated variants. Further structure‐based scoring revealed a hotspot for missense variants in the kinase domain. In addition, to aid future clinical interpretation, we identified the bioinformatics tools best able to differentiate disease associated from nondisease associated variants. We identified GRK1 variants in Oguchi disease patients and investigated how disease‐causing variants may impede protein function in‐silico.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Human Mutation published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | CSNB; GRK1; Oguchi disease; rhodopsin |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Theoretical Physics (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number UKRI (UK Research and Innovation) MR/T02044X/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Dec 2020 14:42 |
Last Modified: | 25 Jun 2023 22:31 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/humu.24140 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168583 |