Poulter, JA;
Gravett, MSC;
Taylor, RL;
Fujinami, K;
De Zaeytijd, J;
Bellingham, J;
Rehman, AU;
... Inglehearn, CF; + view all
(2020)
New variants and in silico analyses in GRK1 associated Oguchi disease.
Human Mutation
10.1002/humu.24140.
(In press).
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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 We identified twelve previously unpublished cases with biallelic disease associated GRK1 variants, including eight novel variants, and reviewed all GRK1 disease associated variants.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.
| Type: | Article |
|---|---|
| Title: | New variants and in silico analyses in GRK1 associated Oguchi disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/humu.24140 |
| Publisher version: | https://doi.org/10.1002/humu.24140 |
| Language: | English |
| Additional information: | Copyright © 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 (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | CSNB, GRK1, Oguchi disease, rhodopsin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10116238 |
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