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Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries

Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliar...

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Autores principales: De Ita, Marlon, Gaytán-Cervantes, Javier, Cisneros, Bulmaro, Araujo, María Antonieta, Huicochea-Montiel, Juan Carlos, Cárdenas-Conejo, Alan, Lazo-Cárdenas, Charles César, Ramírez-Portillo, César Iván, Feria-Kaiser, Carina, Peregrino-Bejarano, Leoncio, Yáñez-Gutiérrez, Lucelli, González-Torres, Carolina, Rosas-Vargas, Haydeé
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498580/
https://www.ncbi.nlm.nih.gov/pubmed/36140829
http://dx.doi.org/10.3390/genes13091662
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author De Ita, Marlon
Gaytán-Cervantes, Javier
Cisneros, Bulmaro
Araujo, María Antonieta
Huicochea-Montiel, Juan Carlos
Cárdenas-Conejo, Alan
Lazo-Cárdenas, Charles César
Ramírez-Portillo, César Iván
Feria-Kaiser, Carina
Peregrino-Bejarano, Leoncio
Yáñez-Gutiérrez, Lucelli
González-Torres, Carolina
Rosas-Vargas, Haydeé
author_facet De Ita, Marlon
Gaytán-Cervantes, Javier
Cisneros, Bulmaro
Araujo, María Antonieta
Huicochea-Montiel, Juan Carlos
Cárdenas-Conejo, Alan
Lazo-Cárdenas, Charles César
Ramírez-Portillo, César Iván
Feria-Kaiser, Carina
Peregrino-Bejarano, Leoncio
Yáñez-Gutiérrez, Lucelli
González-Torres, Carolina
Rosas-Vargas, Haydeé
author_sort De Ita, Marlon
collection PubMed
description Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliary trafficking, as well as genes previously associated with this heart malformation. Deleterious missense and splicing variants of genes DNAH9, DNAH11, and ODAD4 of cilia outer dynein arm and central apparatus, HYDIN, were found in our TGA patients. Remarkable, there is a clustering of deleterious genetic variants in cilia genes, suggesting it could be an oligogenic disease. Our data evidence the genetic diversity and etiological complexity of TGA and point out that population allele determination and genetic aggregation studies are required to improve genetic counseling.
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spelling pubmed-94985802022-09-23 Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries De Ita, Marlon Gaytán-Cervantes, Javier Cisneros, Bulmaro Araujo, María Antonieta Huicochea-Montiel, Juan Carlos Cárdenas-Conejo, Alan Lazo-Cárdenas, Charles César Ramírez-Portillo, César Iván Feria-Kaiser, Carina Peregrino-Bejarano, Leoncio Yáñez-Gutiérrez, Lucelli González-Torres, Carolina Rosas-Vargas, Haydeé Genes (Basel) Article Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliary trafficking, as well as genes previously associated with this heart malformation. Deleterious missense and splicing variants of genes DNAH9, DNAH11, and ODAD4 of cilia outer dynein arm and central apparatus, HYDIN, were found in our TGA patients. Remarkable, there is a clustering of deleterious genetic variants in cilia genes, suggesting it could be an oligogenic disease. Our data evidence the genetic diversity and etiological complexity of TGA and point out that population allele determination and genetic aggregation studies are required to improve genetic counseling. MDPI 2022-09-16 /pmc/articles/PMC9498580/ /pubmed/36140829 http://dx.doi.org/10.3390/genes13091662 Text en © 2022 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 Article
De Ita, Marlon
Gaytán-Cervantes, Javier
Cisneros, Bulmaro
Araujo, María Antonieta
Huicochea-Montiel, Juan Carlos
Cárdenas-Conejo, Alan
Lazo-Cárdenas, Charles César
Ramírez-Portillo, César Iván
Feria-Kaiser, Carina
Peregrino-Bejarano, Leoncio
Yáñez-Gutiérrez, Lucelli
González-Torres, Carolina
Rosas-Vargas, Haydeé
Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries
title Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries
title_full Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries
title_fullStr Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries
title_full_unstemmed Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries
title_short Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries
title_sort clustering of genetic anomalies of cilia outer dynein arm and central apparatus in patients with transposition of the great arteries
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498580/
https://www.ncbi.nlm.nih.gov/pubmed/36140829
http://dx.doi.org/10.3390/genes13091662
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