FHLdb: a comprehensive database on the molecular basis of familial hemophagocytic lymphohistiocytosis

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• dc.contributor.author Viñas Giménez, Laura
• dc.contributor.author Padilla, Natàlia
• dc.contributor.author Batlle Masó, Laura, 1993-
• dc.contributor.author Casals López, Ferran
• dc.contributor.author Rivière, Jacques G.
• dc.contributor.author Martínez-Gallo, Mónica
• dc.contributor.author Cruz, Xavier de la
• dc.contributor.author Colobran, Roger
• dc.date.accessioned 2021-03-17T08:05:49Z
• dc.date.available 2021-03-17T08:05:49Z
• dc.date.issued 2020
• dc.description.abstract Background: Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders. The lack of comprehensive disease-specific mutation databases may hinder or delay classification of the genetic variants found in samples from these patients. This is especially true for familial hemophagocytic lymphohistiocytosis (FHL), a life-threatening PID classically considered an autosomal recessive condition, but with increasingly demonstrated genetic heterogeneity. Objective: The aim of this study was to build an open-access repository to collect detailed information on the known genetic variants reported in FHL. Methods: We manually reviewed more than 120 articles to identify all reported variants related to FHL. We retrieved relevant information about the allelic status, the number of patients with the same variant, and whether functional assays were done. We stored all the data retrieved in a PostgreSQL database and then built a website on top of it, using the Django framework. Results: The database designed (FHLdb) (https://www.biotoclin.org/FHLdb) contains comprehensive information on reported variants in the 4 genes related to FHL (PRF1, UNC13D, STXBP2, STX11). It comprises 240 missense, 69 frameshift, 51 nonsense, 51 splicing, 10 in-frame indel, 7 deep intronic, and 5 large rearrangement variants together with their allelic status, carrier(s) information, and functional evidence. All genetic variants have been classified as pathogenic, likely pathogenic, uncertain significance, likely benign or benign, according to the American College of Medical Genetics guidelines. Additionally, it integrates information from other relevant databases: clinical evidence from ClinVar and UniProt, population allele frequency from ExAC and gnomAD, and pathogenicity predictions from well-recognized tools (e.g., PolyPhen-2, SIFT). Finally, a diagram depicts the location of the variant relative to the gene exon and protein domain structures. Conclusion: FHLdb includes a broad range of data on the reported genetic variants in familial HLH genes. It is a free-access and easy-to-use resource that will facilitate the interpretation of molecular results of FHL patients, and it illustrates the potential value of disease-specific databases for other PIDs.
• dc.description.sponsorship This study was funded by Instituto de Salud Carlos III, grants PI17/00660 and PI18/00346, cofinanced by the European Regional Development Fund (ERDF). LB-M is supported by a Formació de Personal Investigador (FPI) fellowship from Generalitat de Catalunya (2018_FI_B00072). FC was funded by grants SAF2015-68472-C2-2-R from the Ministerio de Economía y Competitividad (Spain) and FEDER (EU) and RTI2018-096824-B-C22 from the Spanish Ministry of Science, Innovation and Universities co-financed by ERDF (FC), and by Direcció General de Recerca, Generalitat de Catalunya (2014SGR-866 and 2017SGR-702).
• dc.format.mimetype application/pdf
• dc.identifier.citation Viñas-Giménez L, Padilla N, Batlle-Masó L, Casals F, Rivière JG, Martínez-Gallo M, de la Cruz X, Colobran R. FHLdb: a comprehensive database on the molecular basis of familial hemophagocytic lymphohistiocytosis. Front Immunol. 2020; 11:107. DOI: 10.3389/fimmu.2020.00107
• dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2020.00107
• dc.identifier.issn 1664-3224
• dc.identifier.uri http://hdl.handle.net/10230/46809
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Immunol. 2020; 11:107
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-68472-C2-2-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096824-B-C22
• dc.rights © 2020 Viñas-Giménez, Padilla, Batlle-Masó, Casals, Rivière, MartínezGallo, de la Cruz and Colobran. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) https://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Database
• dc.subject.keyword Genetic variant
• dc.subject.keyword Genetics
• dc.subject.keyword Hemophagocytic lymphohistiocytosis
• dc.subject.keyword Mutation
• dc.subject.keyword Primary immunodeficiency
• dc.title FHLdb: a comprehensive database on the molecular basis of familial hemophagocytic lymphohistiocytosis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion