Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1.
Hereditary angioedema type 1 (HAE1) is a rare, genetically heterogeneous, and autosomal dominant disease. It is a highly variable, insidious, and potentially life-threatening condition, characterized by sudden local, often asymmetric, and episodic subcutaneous and submucosal swelling, caused by path...
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Public Library of Science (PLoS)
2024-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0311316 |
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| author | Juan Sebastian Arias-Flórez Sandra Ximena Ramirez Bibiana Bayona-Gomez Lina Castro-Castillo Valeria Correa-Martinez Yasmín Sanchez-Gomez William Usaquén-Martínez Lilian Andrea Casas-Vargas Carlos Eduardo Olmos Olmos Nora Contreras Bravo Camilo Andres Velandia-Piedrahita Adrien Morel Rodrigo Cabrera-Perez Natalia Santiago-Tovar Cristian Camilo Gaviria-Sabogal Ingrid Tatyana Bernal Dora Janeth Fonseca-Mendoza Carlos M Restrepo |
| author_facet | Juan Sebastian Arias-Flórez Sandra Ximena Ramirez Bibiana Bayona-Gomez Lina Castro-Castillo Valeria Correa-Martinez Yasmín Sanchez-Gomez William Usaquén-Martínez Lilian Andrea Casas-Vargas Carlos Eduardo Olmos Olmos Nora Contreras Bravo Camilo Andres Velandia-Piedrahita Adrien Morel Rodrigo Cabrera-Perez Natalia Santiago-Tovar Cristian Camilo Gaviria-Sabogal Ingrid Tatyana Bernal Dora Janeth Fonseca-Mendoza Carlos M Restrepo |
| author_sort | Juan Sebastian Arias-Flórez |
| collection | DOAJ |
| description | Hereditary angioedema type 1 (HAE1) is a rare, genetically heterogeneous, and autosomal dominant disease. It is a highly variable, insidious, and potentially life-threatening condition, characterized by sudden local, often asymmetric, and episodic subcutaneous and submucosal swelling, caused by pathogenic molecular variants in the SERPING1 gene, which codes for C1-Inhibitor protein. This study performed the phenotypic and molecular characterization of a HAE1 cluster that includes the largest number of affected worldwide. A geographically HAE1 cluster was found in the northeast Colombian department of Boyaca, which accounts for four unrelated families, with 79 suspected to be affected members. Next-Generation Sequencing (NGS) was performed in 2 out of 4 families (Family 1 and Family 4), identifying the variants c.1420C>T and c.1238T>G, respectively. The latter corresponds to a novel mutation. For Families 2 and 3, the c.1417G>A variant was confirmed by Sanger sequencing. This variant had been previously reported to the patient prior to the beginning of this study. Using deep-learning methods, the structure of the C1-Inhibitor protein, p.Gln474* and p.Met413Arg was predicted, and we propose the molecular mechanism related to the etiology of the disease. Using Sanger sequencing, family segregation analysis was performed on 44 individuals belonging to the families analyzed. The identification of this cluster and its molecular analysis will allow the timely identification of new cases and the establishment of adequate treatment strategies. Our results establish the importance of performing population genetic studies in a multi-cluster region for genetic diseases. |
| format | Article |
| id | doaj-art-8b8496bd612043138833465f94c09b51 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8b8496bd612043138833465f94c09b512025-01-08T05:32:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031131610.1371/journal.pone.0311316Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1.Juan Sebastian Arias-FlórezSandra Ximena RamirezBibiana Bayona-GomezLina Castro-CastilloValeria Correa-MartinezYasmín Sanchez-GomezWilliam Usaquén-MartínezLilian Andrea Casas-VargasCarlos Eduardo Olmos OlmosNora Contreras BravoCamilo Andres Velandia-PiedrahitaAdrien MorelRodrigo Cabrera-PerezNatalia Santiago-TovarCristian Camilo Gaviria-SabogalIngrid Tatyana BernalDora Janeth Fonseca-MendozaCarlos M RestrepoHereditary angioedema type 1 (HAE1) is a rare, genetically heterogeneous, and autosomal dominant disease. It is a highly variable, insidious, and potentially life-threatening condition, characterized by sudden local, often asymmetric, and episodic subcutaneous and submucosal swelling, caused by pathogenic molecular variants in the SERPING1 gene, which codes for C1-Inhibitor protein. This study performed the phenotypic and molecular characterization of a HAE1 cluster that includes the largest number of affected worldwide. A geographically HAE1 cluster was found in the northeast Colombian department of Boyaca, which accounts for four unrelated families, with 79 suspected to be affected members. Next-Generation Sequencing (NGS) was performed in 2 out of 4 families (Family 1 and Family 4), identifying the variants c.1420C>T and c.1238T>G, respectively. The latter corresponds to a novel mutation. For Families 2 and 3, the c.1417G>A variant was confirmed by Sanger sequencing. This variant had been previously reported to the patient prior to the beginning of this study. Using deep-learning methods, the structure of the C1-Inhibitor protein, p.Gln474* and p.Met413Arg was predicted, and we propose the molecular mechanism related to the etiology of the disease. Using Sanger sequencing, family segregation analysis was performed on 44 individuals belonging to the families analyzed. The identification of this cluster and its molecular analysis will allow the timely identification of new cases and the establishment of adequate treatment strategies. Our results establish the importance of performing population genetic studies in a multi-cluster region for genetic diseases.https://doi.org/10.1371/journal.pone.0311316 |
| spellingShingle | Juan Sebastian Arias-Flórez Sandra Ximena Ramirez Bibiana Bayona-Gomez Lina Castro-Castillo Valeria Correa-Martinez Yasmín Sanchez-Gomez William Usaquén-Martínez Lilian Andrea Casas-Vargas Carlos Eduardo Olmos Olmos Nora Contreras Bravo Camilo Andres Velandia-Piedrahita Adrien Morel Rodrigo Cabrera-Perez Natalia Santiago-Tovar Cristian Camilo Gaviria-Sabogal Ingrid Tatyana Bernal Dora Janeth Fonseca-Mendoza Carlos M Restrepo Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1. PLoS ONE |
| title | Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1. |
| title_full | Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1. |
| title_fullStr | Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1. |
| title_full_unstemmed | Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1. |
| title_short | Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1. |
| title_sort | phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1 |
| url | https://doi.org/10.1371/journal.pone.0311316 |
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