New variants and in silico analyses in GRK1 associated Oguchi disease.
Details
Serval ID
serval:BIB_CB7A80BEDE1E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
New variants and in silico analyses in GRK1 associated Oguchi disease.
Journal
Human mutation
Working group(s)
UK Inherited Retinal Disease Consortium, Genomics England Research Consortium
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Publication state
Published
Issued date
02/2021
Peer-reviewed
Oui
Volume
42
Number
2
Pages
164-176
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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 We identified twelve previously unpublished cases with biallelic disease associated GRK1 variants, including eight novel variants, and reviewed all GRK1 disease associated variants.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.
Keywords
Eye Diseases, Hereditary/genetics, G-Protein-Coupled Receptor Kinase 1/genetics, Humans, Night Blindness/genetics, CSNB, GRK1, Oguchi disease, rhodopsin
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2020 15:58
Last modification date
21/04/2023 7:15