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dc.contributor.authorLópez-Lera, Alberto
dc.contributor.authorSanchez-Cabo, Fatima 
dc.contributor.authorGarrido, Sofía
dc.contributor.authorDopazo, Ana 
dc.contributor.authorLópez-Trascasa, Margarita
dc.identifier.citationOrphanet J Rare Dis. 2013; 8(1):77es_ES
dc.description.abstractBACKGROUND: Hereditary Angioedema due to C1-Inhibitor deficiency (HAE types I and II) is a monogenic disease characterized by sudden, self-limited episodes of cutaneous and mucosal swelling due to local deregulation of vascular permeability. Despite its monogenic pattern of inheritance, HAE exhibits great clinical variability and low genotype/phenotype correlation among those affected, which ultimately hinders therapeutic approach and probably underlies yet unknown genetic and environmental factors. METHODS: We studied whole-genome RNA expression of PBMCs in three HAE type-I families (accounting for 40 individuals), 24 of which carry the same R472X mutation in the C1-Inhibitor gene and show large variability in terms of disease expression. Those included in this study were analyzed according to the presence of mutation and/or clinical symptoms. RESULTS: Instead of a single, common disease-associated expression pattern, we found different transcriptome signatures in two of the families studied. In one of them (referred to as DR family), symptoms correlate with the upregulation of 35 genes associated to the biological response to viral infections (including RSADs, OAS, MX and ISG pathway members) and immune response. In another pedigree (Q family), disease manifestation is linked to the upregulation of 43 genes with diverse functions, including transcription and protein folding. Moreover, symptoms-free members of the Q pedigree display relatively higher expression of 394 genes with a wide diversity of functions. CONCLUSION: We found no evidence for a common altered PBMC expression pattern linked to HAE symptoms in the three families analyzed. All the data considered, differential gene expression in PBMCs do not seem to play a significant role in the predisposition or protection against HAE in the basal -between crises- conditions analyzed. Although the RNA expression pattern associated to the response to viral infections observed in the DR family supports the idea of infectious diseases as a modifying factor for HAE severity, large-scale studies would be needed to statistically associate such expression pattern to the development of this rare disease.es_ES
dc.description.sponsorshipThis work has been supported by Centro Investigación Biomédica en Red de Enfermedades Raras, CIBERER (INTRA/09/758,2) and Ministerio de Ciencia e Innovación PI09/00122 and a grant by the Autonomous Region of Madrid (S2010/BMD-2316).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshComplement C1 Inhibitor Protein es_ES
dc.subject.meshFamily es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGene Expression Regulation es_ES
dc.subject.meshHereditary Angioedema Types I and II es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLeukocytes, Mononuclear es_ES
dc.subject.meshMale es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshOligonucleotide Array Sequence Analysis es_ES
dc.subject.meshPedigree es_ES
dc.subject.meshRNA es_ES
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction es_ES
dc.subject.meshGenetic Association Studies es_ES
dc.subject.meshMutation es_ES
dc.titleDisease-modifying factors in hereditary angioedema: an RNA expression-based screeninges_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBERes_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.identifier.journalOrphanet journal of rare diseaseses_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Bioinformáticaes_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Genómicaes_ES

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Atribución 4.0 Internacional
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