Show simple item record

dc.contributor.authorMoreno Izco, Fermín
dc.contributor.authorIndakoetxea Juanbeltz, Begoña
dc.contributor.authorBarandiaran Amillano, Miryam
dc.contributor.authorCaballero, María Cristina
dc.contributor.authorGorostidi, Ana
dc.contributor.authorCalafell, Francesc
dc.contributor.authorGabilondo, Alazne
dc.contributor.authorTainta, Mikel
dc.contributor.authorZulaica, Miren
dc.contributor.authorMartí Massó, José Félix ORCID
dc.contributor.authorLópez de Munain Arregui, Adolfo José
dc.contributor.authorSánchez Juan, Pascual
dc.contributor.authorLee, Suzee E.
dc.date.accessioned2019-05-07T08:39:17Z
dc.date.available2019-05-07T08:39:17Z
dc.date.issued2017-06-08
dc.identifier.citationPlos One 12(6) : (2017) // Article ID e0178093es_ES
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/32666
dc.description.abstractBackground The co-occurrence of the c.709-1G > A GRN mutation and the p.A152T MAPT variant has been identified in 18 Basque families affected by frontotemporal dementia (FTD). We aimed to investigate the influence of the p.A152T MAPT variant on the clinical and neuropathological features of these Basque GRN families. Methods and findings We compared clinical characteristics of 14 patients who carried the c.709-1G > A GRN mutation (GRN+/A152T-) with 21 patients who carried both the c.709-1G > A GRN mutation and the p.A152T MAPT variant (GRN+/A152T+). Neuropsychological data (n = 17) and plasma progranulin levels (n = 23) were compared between groups, and 7 subjects underwent neuropathological studies. We genotyped six short tandem repeat markers in the two largest families. By the analysis of linkage disequilibrium decay in the haplotype block we estimated the time when the first ancestor to carry both genetic variants emerged. GRN+/A152T+ and GRN+/A152T-patients shared similar clinical and neuropsychological features and plasma progranulin levels. All were diagnosed with an FTD disorder, including behavioral variant FTD or non fluent / agrammatic variant primary progressive aphasia, and shared a similar pattern of neuropsychological deficits, predominantly in executive function, memory, and language. All seven participants with available brain autopsies (6 GRN+/A152T+, 1 GRN+/A152T-) showed frontotemporal lobar degeneration with TDP-43 inclusions (type A classification), which is characteristic of GRN carriers. Additionally, all seven showed mild to moderate tau inclusion burden: five cases lacked beta-amyloid pathology and two cases had Alzheimer's pathology. The co-occurrence of both genes within one individual is recent, with the birth of the first GRN+/A152T+ individual estimated to be within the last 50 generations (95% probability). Conclusions In our sample, the p.A152T MAPT variant does not appear to show a discernible influence on the clinical phenotype of GRN carriers. Whether p.A152T confers a greater than expected propensity for tau pathology in these GRN carriers remains an open question.es_ES
dc.description.sponsorshipF.M., P.S.J. and S.E.L. receive funding from the Tau Consortium. F.C. receives funding from the Generalitat de Catalunya (grant 2014 SGR 866). P.S.J. receives funding from ISCIII (PI12/02288). This work was also supported by the Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library Sciencees_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectfrontotemporal lobar degenerationes_ES
dc.subjectC9orf72 repeat expansiones_ES
dc.subjectalzheimers-diseasees_ES
dc.subjectprogranulin mutationes_ES
dc.subjectdementiaes_ES
dc.subjectTaues_ES
dc.subjectvariantes_ES
dc.subjectphenotypeses_ES
dc.subjecthaplotypees_ES
dc.subjectspectrumes_ES
dc.titleThe Unexpected Co-Occurrence of GRN and MAPT p.A152T in Basque Families: Clinical and Pathological Characteristicses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holderThis 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. Attribution 4.0 International (CC BY 4.0)es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178093es_ES
dc.identifier.doi10.1371/journal.pone.0178093
dc.departamentoesNeurocienciases_ES
dc.departamentoeuNeurozientziakes_ES


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

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. Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as 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. Attribution 4.0 International (CC BY 4.0)