New variants and in silico analyses in GRK1 associated Oguchi disease.
CSNB
GRK1
Oguchi disease
rhodopsin
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
26
03
2020
revised:
15
09
2020
accepted:
05
11
2020
pubmed:
1
12
2020
medline:
1
4
2022
entrez:
30
11
2020
Statut:
ppublish
Résumé
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 We identified twelve previously unpublished cases with biallelic disease associated GRK1 variants, including eight novel variants, and reviewed all GRK1 disease associated variants.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.
Identifiants
pubmed: 33252155
doi: 10.1002/humu.24140
pmc: PMC7898643
doi:
Substances chimiques
G-Protein-Coupled Receptor Kinase 1
EC 2.7.11.14
GRK1 protein, human
EC 2.7.11.14
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
164-176Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R024952/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 205041/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Human Mutation published by Wiley Periodicals LLC.
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