Repository logo
 
Publication

Identification of a novel mutation in MEF2C gene in an atypical patient with frontotemporal lobar degeneration

2022-01Journal article Restricted access
Simple item page
dc.contributor.authorAdrião, Andreia
dc.contributor.authorSantana, Isabel
dc.contributor.authorRibeiro, Carolina
dc.contributor.authorCancela, M. Leonor
dc.contributor.authorConceição, Natércia
dc.contributor.authorGrazina, Manuela
dc.date.accessioned2021-09-08T10:57:53Z
dc.date.available2021-09-08T10:57:53Z
dc.date.issued2022-01
dc.description.abstractThe MEF2C gene encodes a transcription factor known to play a crucial role in molecular pathways affecting neuronal development. MEF2C mutations were described as a genetic cause of developmental disease (MRD20), and several reports sustain its involvement in dementia-related conditions, such as Alzheimer's disease and amyotrophic lateral sclerosis. These pathologies and frontotemporal degeneration (FTLD) are thought to share common physiopathological pathways. In this exploratory study, we searched for alterations in the DNA sequence of exons and boundaries, including 5 '- and 3 '-untranslated regions (5 ' UTR, 3 ' UTR), of MEF2C gene in 11 patients with clinical phenotypes related with MRD20 or FTLD. We identified a heterozygous deletion of 13 nucleotides in the 5 ' UTR region of a 69 years old FTLD patient. This alteration was absent in 200 healthy controls, suggesting a contribution to this patient's disease phenotype. In silico analysis of the mutated sequence indicated changes in mRNA secondary structure and stability, thus potentially affecting MEF2C protein levels. Furthermore, in vitro functional analysis of this mutation revealed that the presence of this deletion abolished the transcriptional activity of the gene in human embryonic cells and rat brain neurons, probably by modifying MEF2C expression. Altogether, our results provide evidence for the involvement of MEF2C in FTLD manifesting with seizures.
dc.description.sponsorshipEuropean Regional Development Fund (ERDF) through the COMPETE - Operational Competitiveness Program; FCT Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [PEst-C/SAU/LA0001/2013-2014]
dc.identifier.doi10.1007/s10072-021-05269-0
dc.identifier.issn1590-1874
dc.identifier.urihttp://hdl.handle.net/10400.1/16964
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSPRINGER-VERLAG ITALIA SRL
dc.subjectMental retardation autosomal dominant syndrome-20 disease (MRD20)
dc.subjectFrontotemporal lobar degeneration (FTLD)
dc.subjectMyocyte-specific enhancer factor 2 (MEF2C)
dc.subject5′ Untranslated region (5′UTR)
dc.subject.otherNeurosciences & Neurology
dc.titleIdentification of a novel mutation in MEF2C gene in an atypical patient with frontotemporal lobar degeneration
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/157544/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/COMPETE/PTDC%2FSAU-EPI%2F121811%2F2010/PT
oaire.citation.titleNeurological Sciences
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamCOMPETE
person.familyNameAdrião
person.familyNameCancela
person.familyNameConceição
person.givenNameAndreia Lúcia Gonçalves
person.givenNameM. Leonor
person.givenNameNatércia
person.identifier.ciencia-id7C11-760D-F425
person.identifier.orcid0000-0001-6018-9114
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-5057-0912
person.identifier.scopus-author-id16070252800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublication007689fc-49c0-4a0f-b0d4-1053ec09570d
relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isAuthorOfPublication62064ac0-1f34-407d-96b7-b7074325a84e
relation.isAuthorOfPublication.latestForDiscovery007689fc-49c0-4a0f-b0d4-1053ec09570d
relation.isProjectOfPublicationb4215d8c-d780-4b2e-ae38-d55a36db9755
relation.isProjectOfPublication6ed8e35b-fdeb-4e4b-9d55-0e645c833165
relation.isProjectOfPublication.latestForDiscoveryb4215d8c-d780-4b2e-ae38-d55a36db9755

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Adrião2021_Article_IdentificationOfANovelMutation.pdf
Size:
499.06 KB
Format:
Adobe Portable Document Format
Download

Collections

CCM2-Artigos (em revistas ou actas indexadas)
FCB2-Artigos (em revistas ou actas indexadas)