Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases

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dc.contributor.authorMensa-Vilaro, Anna
dc.contributor.authorGarcía-Morato, María Bravo
dc.contributor.authorCalle-Martin, Oscar de la
dc.contributor.authorFranco-Jarava, Clara
dc.contributor.authorMartínez de Saavedra Álvarez, María Teresa
dc.contributor.authorGonzalez-Granado, Luis Ignacio
dc.contributor.authorGonzalez-Roca, Eva
dc.contributor.authorGarcia Fuster, José Luís
dc.contributor.authorAlsina, Laia
dc.contributor.authorMutchinick, Osvaldo M.
dc.contributor.authorBalderrama-Rodríguez, Angélica
dc.contributor.authorRamos, Eduardo
dc.contributor.authorModesto Caballero, Consuelo
dc.contributor.authorGõmez-de la Fuente, Enrique
dc.contributor.authorBravo Gallego, Luz Yadira
dc.contributor.authorCampistol, Joseph María
dc.contributor.authorGuirat Dhouib, Nawel
dc.contributor.authorBéjaoui, Mohamed
dc.contributor.authorDutra, Lívia Almeida
dc.contributor.authorTerreri, Maria Teresa
dc.contributor.authorMosquera, Catalina
dc.contributor.authorGonzález, Tatiana
dc.contributor.authorCañellas, Jerónima
dc.contributor.authorGarcía Ruíz de Morales, José María
dc.contributor.authorWouters, Carine
dc.contributor.authorBosque, María Teresa
dc.contributor.authorWeng Tarng, Cham
dc.contributor.authorJiménez-Treviño, Santiago S.
dc.contributor.authorDe Inocencio, Jaime
dc.contributor.authorBloomfield, Markéta
dc.contributor.authorPérez de Diego, Rebeca
dc.contributor.authorMartínez-Pomar, Natalia
dc.contributor.authorRodríguez-Pena, Rebeca
dc.contributor.authorGonzález-Santesteban, Cecilia
dc.contributor.authorSoler-Palacin, Pere
dc.contributor.authorCasals, Ferran
dc.contributor.authorYagúe, Jordi L.
dc.contributor.authorAllende, Luís Miguel
dc.contributor.authorRodríguez-Gallego, José Carlos
dc.contributor.authorColobran, Roger
dc.contributor.authorMartínez-Martínez, Laura
dc.contributor.authorLópez-Granados, Eduardo
dc.contributor.authorArostegui, Juan Ignacio
dc.date.accessioned2020-05-11T17:29:59Z
dc.date.available2020-05-11T17:29:59Z
dc.date.issued2019
dc.description.abstractenglishBackground Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. Objective We sought to investigate the incidence of gene mosaicism in patients with PIDs. Methods The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. Results The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. Conclusion This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing–based methods in the routine analyses of PIDs.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1016/j.jaci.2018.09.009
dc.identifier.issn1097-6825
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2551
dc.language.isoeng
dc.publisherElsevierspa
dc.publisher.journalJournal of allergy and clinical immunologyspa
dc.relation.ispartofseriesJournal of allergy and clinical immunology, 1097-6825, Vol. 143, Nro. 1, 2019, p. 359-368spa
dc.relation.urihttps://www.jacionline.org/article/S0091-6749(18)31358-7/fulltext
dc.rights.creativecommons2019
dc.rights.localAcceso cerradospa
dc.subject.decsEnfermedades autoinflamatorias hereditariasspa
dc.subject.decsGenéticaspa
dc.subject.decsGenotipospa
dc.subject.keywordsPostzygotic variantsspa
dc.subject.keywordsGene mosaicismspa
dc.subject.keywordsPrimary immunodeficiency deseasesspa
dc.titleUnexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseasesspa
dc.title.translatedUnexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseasesspa
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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