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...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2024
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/44705
- Acceso en línea:
- https://doi.org/10.1371/journal.pone.0311316
https://repository.urosario.edu.co/handle/10336/44705
- Palabra clave:
- Hereditary angioedema type 1
SERPING1 gene
C1 Inhibitor phenotypes
C1 Inhibitor phenotypes
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- License
- Attribution-NonCommercial-ShareAlike 4.0 International
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Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1 |
| title |
Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1 |
| spellingShingle |
Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1 Hereditary angioedema type 1 SERPING1 gene C1 Inhibitor phenotypes C1 Inhibitor phenotypes |
| title_short |
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_sort |
Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1 |
| dc.contributor.gruplac.none.fl_str_mv |
Genética Evolutiva, Filogeografía y Ecología de Biodiversidad Neotropical |
| dc.subject.none.fl_str_mv |
Hereditary angioedema type 1 SERPING1 gene C1 Inhibitor phenotypes |
| topic |
Hereditary angioedema type 1 SERPING1 gene C1 Inhibitor phenotypes C1 Inhibitor phenotypes |
| dc.subject.keyword.none.fl_str_mv |
C1 Inhibitor phenotypes |
| 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. NextGeneration 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. |
| publishDate |
2024 |
| dc.date.created.none.fl_str_mv |
2024-12-18 |
| dc.date.issued.none.fl_str_mv |
2024-12-26 |
| dc.date.accessioned.none.fl_str_mv |
2025-01-16T02:12:49Z |
| dc.date.available.none.fl_str_mv |
2025-01-16T02:12:49Z |
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article |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://purl.org/coar/resource_type/c_6501 |
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Artículo |
| dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1371/journal.pone.0311316 |
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https://repository.urosario.edu.co/handle/10336/44705 |
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https://doi.org/10.1371/journal.pone.0311316 https://repository.urosario.edu.co/handle/10336/44705 |
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eng |
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eng |
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https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0311316 |
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Attribution-NonCommercial-ShareAlike 4.0 International |
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http://purl.org/coar/access_right/c_abf2 |
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Abierto (Texto completo) |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ |
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Attribution-NonCommercial-ShareAlike 4.0 International Abierto (Texto completo) http://creativecommons.org/licenses/by-nc-sa/4.0/ http://purl.org/coar/access_right/c_abf2 |
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19 pp |
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application/pdf |
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Universidad del Rosario |
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Busse PJ, Christiansen SC. Hereditary Angioedema. Longo DL, editor. N Engl J Med. 2020 Mar 19; 382(12):1136–48. https://doi.org/10.1056/NEJMra1808012 PMID: 32187470 Nieto S, Madrigal I, Contreras F, Vargas ME. Real-world experience of hereditary angioedema (HAE) in Mexico: A mixed-methods approach to describe epidemiology, diagnosis, and treatment patterns. World Allergy Organization Journal. 2023 Sep; 16(9):100812. https://doi.org/10.1016/j.waojou.2023. 100812 PMID: 37727628 Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygo¨ren-Pu¨rsu¨n E, et al. The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update. Allergy. 2022 Jul; 77(7):1961–90. https://doi.org/10.1111/all.15214 PMID: 35006617 Branco Ferreira M, Baeza M, Spı´nola Santos A, Prieto-Garcı´a A, Leal R, Alvarez J, et al. Evolution of Guidelines for the Management of Hereditary Angioedema due to C1 Inhibitor Deficiency. J Investig Allergol Clin. 2023 Oct 11; 33(5):332–62. https://doi.org/10.18176/jiaci.0909 PMID: 37171188 Ponard D, Gaboriaud C, Charignon D, Ghannam A, Wagenaar-Bos IGA, Roem D, et al. SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes. Human Mutation. 2020 Jan; 41 (1):38–57. https://doi.org/10.1002/humu.23917 PMID: 31517426 Germenis AE, Speletas M. Genetics of Hereditary Angioedema Revisited. Clinic Rev Allerg Immunol. 2016 Oct; 51(2):170–82. Giavina-Bianchi P, Vivolo Aun M, Giavina-Bianchi M, Ribeiro AJ, Camara Agondi R, Motta AA, et al. Hereditary angioedema classification: Expanding knowledge by genotyping and endotyping. World Allergy Organization Journal. 2024 May; 17(5):100906. https://doi.org/10.1016/j.waojou.2024.100906 PMID: 38818086 Fabiani J, Valle SOR, Olivares M, Nieto S, Landeros EH, Ginaca A, et al. Improving C1 inhibitor deficiency (type 1 and type 2 hereditary angioedema) in Latin America. J Investig Allergol Clin Immunol. 2014; 24(6):445–7. PMID: 25668899 Olivares MM, Farfan R, Olmos CE, Gomez C, Sanchez J, Ortega-Lopez MC, et al. Report of Colombian Registry for Hereditary Angioedema. Journal of Allergy and Clinical Immunology. 2016 Feb;137(2): AB248. Sa´nchez MD, Cuervo J, Rave D, Clemen G, Yepes JJ, Ortiz-Reyes B, et al. Angioedema hereditario en Medellı´n, Colombia: evaluacio´n clı´nica y de la calidad de vida. biomedica [Internet]. 2015 May 13 [cited 2024 Sep 2];35(3). Available from: http://www.revistabiomedica.org/index.php/biomedica/article/view/ 2417 Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine. 2015 May; 17(5):405–24. https://doi.org/10.1038/gim.2015.30 PMID: 25741868 Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug 26; 596(7873):583–9. https://doi.org/10.1038/s41586- 021-03819-2 PMID: 34265844 Du Z, Su H, Wang W, Ye L, Wei H, Peng Z, et al. The trRosetta server for fast and accurate protein structure prediction. Nat Protoc. 2021 Dec; 16(12):5634–51. https://doi.org/10.1038/s41596-021- 00628-9 PMID: 34759384 Cheng J, Novati G, Pan J, Bycroft C, Zˇemgulytė A, Applebaum T, et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science. 2023 Sep 22; 381(6664):eadg7492. https://doi.org/10.1126/science.adg7492 PMID: 37733863 Rodrigues CHM, Pires DEV, Ascher DB. DYNAMUT2: Assessing changes in stability and flexibility upon single and multiple point missense mutations. Protein Science. 2021 Jan; 30(1):60–9 . Goddard TD, Huang CC, Meng EC, Pettersen EF, Couch GS, Morris JH, et al. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Science. 2018 Jan; 27(1):14–25. https:// doi.org/10.1002/pro.3235 PMID: 28710774 Drouet C, Lo´pez-Lera A, Ghannam A, Lo´pez-Trascasa M, Cichon S, Ponard D, et al. SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE. Front Allergy. 2022 Mar 31; 3:835503. Sistema Estadistico Nacional. LA INFORMACIO´ N DEL DANE EN LA TOMA DE DECISIONES DE LAS CIUDADES CAPITALES [Internet]. DANE; 2021. Available from: https://www.dane.gov.co/files/ investigaciones/planes-departamentos-ciudades/210209-InfoDane-Tunja-Boyaca.pdf Lumry WR, Settipane RA. Hereditary angioedema: Epidemiology and burden of disease. Allergy Asthma Proc. 2020 Nov 1; 41(Suppl 1):S08–S13. https://doi.org/10.2500/aap.2020.41.200050 PMID: 33109318 Pacheco-Orozco RA, Torres LJ, Velasco HM. Determinacio´n de endogamia mediante me´todo de isonimia en la poblacio´n de Runta, Boyaca´, Colombia. Rev Fac Med. 2019 Apr 1; 67(2):241–5 Cardoso-dos-Santos AC, Reales G, Schuler-Faccini L. Clusters of rare disorders and congenital anomalies in South America. Revista Panamericana de Salud Pu´blica. 2023 Jun 23; 47:1. https://doi.org/10. 26633/RPSP.2023.98 PMID: 37363626 Velasco H, Galvis J, Martin AM, Buelvas L, Sanchez J, Umaña LA, et al. Gene´tica clı´nica comunitaria: exploracio´n de patologı´a gene´tica en Boyaca´, Colombia. Rev salud pu´blica. 2017 Jan 1; 19(1):32–8 Pachajoa H, Acosta MA, Alme´ciga-Dı´az CJ, Ariza Y, Diaz-Ordoñez L, Caicedo-Herrera G, et al. Molecular characterization of mucopolysaccharidosis type IVA patients in the Andean region of Colombia. American J of Med Genetics Pt C. 2021 Sep; 187(3):388–95. Arcos-Burgos M, Muenke M. Genetics of population isolates. Clinical Genetics. 2002 Apr; 61(4):233– 47. https://doi.org/10.1034/j.1399-0004.2002.610401.x PMID: 12030885 Passos-Bueno MR, Bertola D, Horovitz DDG, De Faria Ferraz VE, Brito LA. Genetics and genomics in Brazil: a promising future. Molec Gen & Gen Med. 2014 Jul; 2(4):280–91. Wang X, Lei S, Xu Y, Liu S, Zhi Y. Mutation update of SERPING1 related to hereditary angioedema in the Chinese population. Hereditas. 2022 Dec; 159(1):28. https://doi.org/10.1186/s41065-022-00242-z PMID: 35821062 |
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Genética Evolutiva, Filogeografía y Ecología de Biodiversidad NeotropicalArias-Flórez, Juan SebastianRamírez, Sandra XimenaBayona-Gomez, BibianaCastro-Castillo, LinaCorrea-Martínez, ValeriaSánchez-Gomez, YasminUsaquén.Martínez, WilliamCasas Vargas, Lilian-AndreaOlmos Olmos, Carlos EduardoContreras Barvo, NoraVelandia-Piedrahita, Camilo AndresMorel, AdrienCabrera-Perez, RodrigoSantiago-Tovar, NataliaGaviria-Sabogal, Cristian CamiloBernal, Ingrid TatyanaFonseca-Mendoza, Dora JanethRestrepo, Carlos M.2249a7be-6223-4ee3-8987-7baddc3bacde-14849628d-2616-48db-a74e-745735fc36b3-18eb38b94-8ca7-40d3-b703-d5375a343ea6-151a38541-53b9-46fe-92a5-3cbe35f7f9d8-1fecf3f7d-1db6-4bc6-b73e-0ab5053b6cc19f8dc8b7-e56c-4905-8095-55f274794038-153b67204-6fd7-4d6a-afec-e50d0365f693-1eb6ff655-4a9c-4db9-b11b-526036c197c0-11eee2134-4d4e-47e1-8695-4a465600618a-19060a992-f1eb-4b90-9c26-313e372c8bbe-1c3e6bbfd-e4b7-43b0-bd63-1140aa460396-168277860066e159ab-a660-41d7-9472-2ba820ac9b01-184221cc1-a1d9-47b4-81c2-98d8e59a4763-1f4a57ac3-6a71-4e2f-8819-fa39ce825c40-1586c8832-1f32-4343-a925-b5112eaae82b-1c0988714-00b0-4916-8293-62751e129ec8-119331819-12025-01-16T02:12:49Z2025-01-16T02:12:49Z2024-12-182024-12-26Hereditary 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. NextGeneration 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.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. NextGeneration 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.19 ppapplication/pdfBoyacahttps://doi.org/10.1371/journal.pone.0311316https://repository.urosario.edu.co/handle/10336/44705enghttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0311316Attribution-NonCommercial-ShareAlike 4.0 InternationalAbierto (Texto completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo habeasdata@urosario.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datos.http://creativecommons.org/licenses/by-nc-sa/4.0/http://purl.org/coar/access_right/c_abf2Busse PJ, Christiansen SC. Hereditary Angioedema. Longo DL, editor. N Engl J Med. 2020 Mar 19; 382(12):1136–48. https://doi.org/10.1056/NEJMra1808012 PMID: 32187470Nieto S, Madrigal I, Contreras F, Vargas ME. Real-world experience of hereditary angioedema (HAE) in Mexico: A mixed-methods approach to describe epidemiology, diagnosis, and treatment patterns. World Allergy Organization Journal. 2023 Sep; 16(9):100812. https://doi.org/10.1016/j.waojou.2023. 100812 PMID: 37727628Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygo¨ren-Pu¨rsu¨n E, et al. The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update. Allergy. 2022 Jul; 77(7):1961–90. https://doi.org/10.1111/all.15214 PMID: 35006617Branco Ferreira M, Baeza M, Spı´nola Santos A, Prieto-Garcı´a A, Leal R, Alvarez J, et al. Evolution of Guidelines for the Management of Hereditary Angioedema due to C1 Inhibitor Deficiency. J Investig Allergol Clin. 2023 Oct 11; 33(5):332–62. https://doi.org/10.18176/jiaci.0909 PMID: 37171188Ponard D, Gaboriaud C, Charignon D, Ghannam A, Wagenaar-Bos IGA, Roem D, et al. SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes. Human Mutation. 2020 Jan; 41 (1):38–57. https://doi.org/10.1002/humu.23917 PMID: 31517426Germenis AE, Speletas M. Genetics of Hereditary Angioedema Revisited. Clinic Rev Allerg Immunol. 2016 Oct; 51(2):170–82.Giavina-Bianchi P, Vivolo Aun M, Giavina-Bianchi M, Ribeiro AJ, Camara Agondi R, Motta AA, et al. Hereditary angioedema classification: Expanding knowledge by genotyping and endotyping. World Allergy Organization Journal. 2024 May; 17(5):100906. https://doi.org/10.1016/j.waojou.2024.100906 PMID: 38818086Fabiani J, Valle SOR, Olivares M, Nieto S, Landeros EH, Ginaca A, et al. Improving C1 inhibitor deficiency (type 1 and type 2 hereditary angioedema) in Latin America. J Investig Allergol Clin Immunol. 2014; 24(6):445–7. PMID: 25668899Olivares MM, Farfan R, Olmos CE, Gomez C, Sanchez J, Ortega-Lopez MC, et al. Report of Colombian Registry for Hereditary Angioedema. Journal of Allergy and Clinical Immunology. 2016 Feb;137(2): AB248.Sa´nchez MD, Cuervo J, Rave D, Clemen G, Yepes JJ, Ortiz-Reyes B, et al. Angioedema hereditario en Medellı´n, Colombia: evaluacio´n clı´nica y de la calidad de vida. biomedica [Internet]. 2015 May 13 [cited 2024 Sep 2];35(3). Available from: http://www.revistabiomedica.org/index.php/biomedica/article/view/ 2417Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine. 2015 May; 17(5):405–24. https://doi.org/10.1038/gim.2015.30 PMID: 25741868Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug 26; 596(7873):583–9. https://doi.org/10.1038/s41586- 021-03819-2 PMID: 34265844Du Z, Su H, Wang W, Ye L, Wei H, Peng Z, et al. The trRosetta server for fast and accurate protein structure prediction. Nat Protoc. 2021 Dec; 16(12):5634–51. https://doi.org/10.1038/s41596-021- 00628-9 PMID: 34759384Cheng J, Novati G, Pan J, Bycroft C, Zˇemgulytė A, Applebaum T, et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science. 2023 Sep 22; 381(6664):eadg7492. https://doi.org/10.1126/science.adg7492 PMID: 37733863Rodrigues CHM, Pires DEV, Ascher DB. DYNAMUT2: Assessing changes in stability and flexibility upon single and multiple point missense mutations. Protein Science. 2021 Jan; 30(1):60–9. Goddard TD, Huang CC, Meng EC, Pettersen EF, Couch GS, Morris JH, et al. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Science. 2018 Jan; 27(1):14–25. https:// doi.org/10.1002/pro.3235 PMID: 28710774Drouet C, Lo´pez-Lera A, Ghannam A, Lo´pez-Trascasa M, Cichon S, Ponard D, et al. SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE. Front Allergy. 2022 Mar 31; 3:835503.Sistema Estadistico Nacional. LA INFORMACIO´ N DEL DANE EN LA TOMA DE DECISIONES DE LAS CIUDADES CAPITALES [Internet]. DANE; 2021. Available from: https://www.dane.gov.co/files/ investigaciones/planes-departamentos-ciudades/210209-InfoDane-Tunja-Boyaca.pdfLumry WR, Settipane RA. 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