FHLdb : A Comprehensive Database on the Molecular Basis of Familial Hemophagocytic Lymphohistiocytosis
Viñas-Giménez, Laura (Jeffrey Model Foundation Excellence Center)
Padilla Sirera, Natàlia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Batlle-Masó, Laura (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Casals, Ferran (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Rivière, Jacques G.. (Jeffrey Model Foundation Excellence Center)
Martínez Gallo, Mónica (Jeffrey Model Foundation Excellence Center)
de la Cruz, Xavier (Institució Catalana de Recerca i Estudis Avançats)
Colobrán Oriol, Roger (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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) () 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.
Ajuts:	Instituto de Salud Carlos III PI17-00660 Instituto de Salud Carlos III PI18-00346 Ministerio de Economía y Competitividad SAF2015-68472-C2-2-R Ministerio de Ciencia e Innovación RTI2018-096824-B-C22 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018_FI_B00072 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-866 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-702
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Primary immunodeficiency ; Hemophagocytic lymphohistiocytosis ; Database ; Genetics ; Mutation ; Genetic variant
Publicat a:	Frontiers in immunology, Vol. 11 (january 2020) , ISSN 1664-3224

DOI: 10.3389/fimmu.2020.00107
PMID: 32076423

1.4 MB

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