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

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dc.contributor.advisorRestrepo Fernández, Carlos Martin
dc.contributor.gruplacGrupo de Neurociencias de la Universidad del Rosario (NEUROS)
dc.creatorArias-Flórez, Juan Sebastian
dc.creatorRamírez Jiménez, Sandra Ximena
dc.creatorBayona Gómez, Bibiana
dc.creatorCastro Castillo, Lina
dc.creatorCorrea-Martinez, Valeria
dc.creatorSanchez-Gomez, Yasmín
dc.creatorUsaquén-Martínez, William
dc.creatorCasas-Vargas, Lilian Andrea
dc.creatorOlmos Olmos, Carlos Eduardo
dc.creatorContreras Bravo, 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.creator.degreeEspecialista en Neonatología
dc.creator.degreeLevelMaestría
dc.date.accessioned2025-05-27T19:36:54Z
dc.date.available2025-05-27T19:36:54Z
dc.date.created2024-12-26
dc.date.embargoEndinfo:eu-repo/date/embargoEnd/2027-05-28
dc.descriptionEl angioedema hereditario tipo 1 (AEH1) es una enfermedad rara, genéticamente heterogénea y autosómica dominante. Es una afección altamente variable, insidiosa y potencialmente mortal, caracterizada por una hinchazón subcutánea y submucosa local repentina, a menudo asimétrica y episódica, causada por variantes moleculares patógenas en el gen SERPING1, que codifica la proteína inhibidora de C1. Este estudio realizó la caracterización fenotípica y molecular de un grupo de AEH1 que incluye el mayor número de afectados a nivel mundial. Se encontró un grupo geográfico de AEH1 en el departamento de Boyacá, al noreste de Colombia, que comprende cuatro familias no relacionadas, con 79 miembros sospechosos de estar afectados. Se realizó secuenciación de nueva generación (NGS) en 2 de las 4 familias (Familia 1 y Familia 4), identificando las variantes c.1420C>T y c.1238T>G, respectivamente. Esta última corresponde a una mutación novedosa. Para las familias 2 y 3, la variante c.1417G>A se confirmó mediante secuenciación de Sanger. Esta variante ya se había notificado al paciente antes del inicio de este estudio. Mediante métodos de aprendizaje profundo, se predijo la estructura de la proteína inhibidora de C1, p.Gln474* y p.Met413Arg, y se propuso el mecanismo molecular relacionado con la etiología de la enfermedad. Mediante secuenciación de Sanger, se realizó un análisis de segregación familiar en 44 individuos pertenecientes a las familias analizadas. La identificación de este clúster y su análisis molecular permitirá la identificación oportuna de nuevos casos y el establecimiento de estrategias de tratamiento adecuadas. Nuestros resultados demuestran la importancia de realizar estudios genéticos poblacionales en una región multiclúster para las enfermedades genéticas.
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. 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.
dc.format.extent30 pp
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.48713/10336_45396
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/45396
dc.language.isospa
dc.publisherUniversidad del Rosario
dc.publisher.departmentEscuela de Medicina y Ciencias de la Salud
dc.publisher.programEspecialización en Neonatología
dc.relation.relatedhttps://doi.org/10.1371/journal.pone.0311316
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dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectAngioedema hereditario
dc.subjectEndogamia
dc.subjectEnfermedades geneticas
dc.subject.keywordHereditary angioedema
dc.subject.keywordGenetic diseases
dc.subject.keywordEndogamy
dc.titlePhenotypic and molecular characterization of the largest worldwide cluster of hereditary angioedema type 1
dc.title.TranslatedTitleCaracterización fenotípica y molecular de el mayor grupo mundial de enfermedades hereditarias angioedema tipo 1
dc.typemasterThesis
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaArtículo
local.department.reportEscuela de Medicina y Ciencias de la Salud
local.regionesBogotá
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