Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?
dc.contributor.author | Urrutia, Inés | |
dc.contributor.author | Martínez Salazar, Rosa | |
dc.contributor.author | Rica, Itxaso | |
dc.contributor.author | Martínez de la Piscina Martín, Idoia | |
dc.contributor.author | García Castaño, Alejandro | |
dc.contributor.author | Aguayo Calcena, Aníbal | |
dc.contributor.author | Calvo, Begoña | |
dc.contributor.author | Castaño González, Luis Antonio ![]() | |
dc.contributor.author | Spanish Pediatric Diabetes Collaborative Group | |
dc.date.accessioned | 2020-01-31T09:06:12Z | |
dc.date.available | 2020-01-31T09:06:12Z | |
dc.date.issued | 2019-07-31 | |
dc.identifier.citation | Plos One 14(7) : (2019) // Article ID e0220634 | es_ES |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/39755 | |
dc.description.abstract | Objective Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis. Methods Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 +/- 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing. Results ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity. Conclusion ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study. | es_ES |
dc.description.sponsorship | This work was partially supported by grants from Menarini Group Spain (BCA/16/030), University of the Basque Country, UPV/EHU (IT795-13), Department of Health of the Basque Government (GV2016111035) and ISCIII (PI14/01104) integrated into the National R&D&I Plan 2013-2016 and co-financed by FEDER (European Funds for Regional Development). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library Science | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | insulin gene-mutations | es_ES |
dc.subject | rare variants | es_ES |
dc.subject | young mody | es_ES |
dc.subject | onset | es_ES |
dc.subject | children | es_ES |
dc.subject | mellitus | es_ES |
dc.subject | adolescents | es_ES |
dc.subject | autoantibodies | es_ES |
dc.subject | diagnosis | es_ES |
dc.subject | age | es_ES |
dc.title | Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes? | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2019 Urrutia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220634 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0220634 | |
dc.departamentoes | Medicina | es_ES |
dc.departamentoeu | Medikuntza | es_ES |
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Except where otherwise noted, this item's license is described as © 2019 Urrutia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.