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Phenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1

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dc.contributor.gruplacGenética Evolutiva, Filogeografía y Ecología de Biodiversidad Neotropical
dc.creatorArias-Flórez, Juan Sebastian
dc.creatorRamírez, Sandra Ximena
dc.creatorBayona-Gomez, Bibiana
dc.creatorCastro-Castillo, Lina
dc.creatorCorrea-Martínez, Valeria
dc.creatorSánchez-Gomez, Yasmin
dc.creatorUsaquén.Martínez, William
dc.creatorCasas Vargas, Lilian-Andrea
dc.creatorOlmos Olmos, Carlos Eduardo
dc.creatorContreras Barvo, Nora
dc.creatorVelandia-Piedrahita, Camilo Andres
dc.creatorMorel, Adrien
dc.creatorCabrera-Perez, Rodrigo
dc.creatorSantiago-Tovar, Natalia
dc.creatorGaviria-Sabogal, Cristian Camilo
dc.creatorBernal, Ingrid Tatyana
dc.creatorFonseca-Mendoza, Dora Janeth
dc.creatorRestrepo, Carlos M.
dc.date.accessioned2025-01-16T02:12:49Z
dc.date.available2025-01-16T02:12:49Z
dc.date.created2024-12-18
dc.date.issued2024-12-26
dc.descriptionHereditary 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.
dc.description.abstractHereditary 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.
dc.format.extent19 pp
dc.format.mimetypeapplication/pdf
dc.geoLocationBoyaca
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0311316
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/44705
dc.language.isoeng
dc.relation.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0311316
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dc.source.bibliographicCitationBusse 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
dc.source.bibliographicCitationNieto 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
dc.source.bibliographicCitationMaurer 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
dc.source.bibliographicCitationBranco 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
dc.source.bibliographicCitationPonard 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
dc.source.bibliographicCitationGermenis AE, Speletas M. Genetics of Hereditary Angioedema Revisited. Clinic Rev Allerg Immunol. 2016 Oct; 51(2):170–82.
dc.source.bibliographicCitationGiavina-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
dc.source.bibliographicCitationFabiani 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
dc.source.bibliographicCitationOlivares 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.
dc.source.bibliographicCitationSa´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
dc.source.bibliographicCitationRichards 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
dc.source.bibliographicCitationJumper 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
dc.source.bibliographicCitationDu 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
dc.source.bibliographicCitationCheng 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
dc.source.bibliographicCitationRodrigues 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
dc.source.bibliographicCitation. 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
dc.source.bibliographicCitationDrouet 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.
dc.source.bibliographicCitationSistema 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
dc.source.bibliographicCitationLumry 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
dc.source.bibliographicCitationPacheco-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
dc.source.bibliographicCitationCardoso-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
dc.source.bibliographicCitationVelasco 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
dc.source.bibliographicCitationPachajoa 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.
dc.source.bibliographicCitationArcos-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
dc.source.bibliographicCitationPassos-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.
dc.source.bibliographicCitationWang 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
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectHereditary angioedema type 1
dc.subjectSERPING1 gene
dc.subjectC1 Inhibitor phenotypes
dc.subject.keywordC1 Inhibitor phenotypes
dc.titlePhenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1
dc.typearticle
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículo
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