Cargando…

Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2) a...

Descripción completa

Detalles Bibliográficos
Autores principales: Amaral, Rebeca A. S., Motta, Fabiana L., Zin, Olivia A., da Palma, Mariana M., Rodrigues, Gabriela D., Sallum, Juliana M. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298554/
https://www.ncbi.nlm.nih.gov/pubmed/37372476
http://dx.doi.org/10.3390/genes14061296
_version_ 1785064144775413760
author Amaral, Rebeca A. S.
Motta, Fabiana L.
Zin, Olivia A.
da Palma, Mariana M.
Rodrigues, Gabriela D.
Sallum, Juliana M. F.
author_facet Amaral, Rebeca A. S.
Motta, Fabiana L.
Zin, Olivia A.
da Palma, Mariana M.
Rodrigues, Gabriela D.
Sallum, Juliana M. F.
author_sort Amaral, Rebeca A. S.
collection PubMed
description Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2) and of the unfolded protein response (ATF6) have been related to ACHM cases, while CNGA3 and CNGB3 alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the CNGA3 and CNGB3 genes. Patients’ genotype and phenotype were retrospectively evaluated. The majority of CNGA3 variants were missense, and the most prevalent CNGB3 variant was c.1148delC (p.Thr383Ilefs*13), resulting in a frameshift and premature stop codon, which is compatible with previous publications in the literature. A novel variant c.1893T>A (p.Tyr631*) in the CNGB3 gene is reported for the first time in this study. A great variability in morphologic findings was observed in our patients, although no consistent correlation with age and disease stage in OCT foveal morphology was found. The better understanding of the genetic variants landscape in the Brazilian population will help in the diagnosis of this disease.
format Online
Article
Text
id pubmed-10298554
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102985542023-06-28 Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia Amaral, Rebeca A. S. Motta, Fabiana L. Zin, Olivia A. da Palma, Mariana M. Rodrigues, Gabriela D. Sallum, Juliana M. F. Genes (Basel) Brief Report Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2) and of the unfolded protein response (ATF6) have been related to ACHM cases, while CNGA3 and CNGB3 alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the CNGA3 and CNGB3 genes. Patients’ genotype and phenotype were retrospectively evaluated. The majority of CNGA3 variants were missense, and the most prevalent CNGB3 variant was c.1148delC (p.Thr383Ilefs*13), resulting in a frameshift and premature stop codon, which is compatible with previous publications in the literature. A novel variant c.1893T>A (p.Tyr631*) in the CNGB3 gene is reported for the first time in this study. A great variability in morphologic findings was observed in our patients, although no consistent correlation with age and disease stage in OCT foveal morphology was found. The better understanding of the genetic variants landscape in the Brazilian population will help in the diagnosis of this disease. MDPI 2023-06-20 /pmc/articles/PMC10298554/ /pubmed/37372476 http://dx.doi.org/10.3390/genes14061296 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Amaral, Rebeca A. S.
Motta, Fabiana L.
Zin, Olivia A.
da Palma, Mariana M.
Rodrigues, Gabriela D.
Sallum, Juliana M. F.
Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
title Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
title_full Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
title_fullStr Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
title_full_unstemmed Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
title_short Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia
title_sort molecular and clinical characterization of cnga3 and cngb3 genes in brazilian patients affected with achromatopsia
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298554/
https://www.ncbi.nlm.nih.gov/pubmed/37372476
http://dx.doi.org/10.3390/genes14061296
work_keys_str_mv AT amaralrebecaas molecularandclinicalcharacterizationofcnga3andcngb3genesinbrazilianpatientsaffectedwithachromatopsia
AT mottafabianal molecularandclinicalcharacterizationofcnga3andcngb3genesinbrazilianpatientsaffectedwithachromatopsia
AT zinoliviaa molecularandclinicalcharacterizationofcnga3andcngb3genesinbrazilianpatientsaffectedwithachromatopsia
AT dapalmamarianam molecularandclinicalcharacterizationofcnga3andcngb3genesinbrazilianpatientsaffectedwithachromatopsia
AT rodriguesgabrielad molecularandclinicalcharacterizationofcnga3andcngb3genesinbrazilianpatientsaffectedwithachromatopsia
AT sallumjulianamf molecularandclinicalcharacterizationofcnga3andcngb3genesinbrazilianpatientsaffectedwithachromatopsia