Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia.
CNGA3
achromatopsia
cyclic nucleotide-gated ion channel
in silico analysis
variant classification
variant spectrum
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
23
02
2022
received:
13
08
2021
accepted:
22
03
2022
pubmed:
26
3
2022
medline:
10
6
2022
entrez:
25
3
2022
Statut:
ppublish
Résumé
Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying "likely disease-causing" variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as "likely disease-causing" according to ACMG/AMP criteria. We report 48 novel "likely disease-causing" variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.
Substances chimiques
CNGA3 protein, human
0
Cyclic Nucleotide-Gated Cation Channels
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
832-858Subventions
Organisme : NEI NIH HHS
ID : R24 EY028758
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY018213
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG050437
Pays : United States
Organisme : NEI NIH HHS
ID : U01 EY030580
Pays : United States
Organisme : NEI NIH HHS
ID : R24 EY027285
Pays : United States
Organisme : NIH HHS
ID : U54 OD020351
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY033770
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024698
Pays : United States
Informations de copyright
© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.
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