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Definition of a putative pathological region in PARK2 associated with autism spectrum disorder through in silico analysis of its functional structure

2016-11-07Journal article Restricted access
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dc.contributor.authorConceição, I.C.
dc.contributor.authorRama, M.M.
dc.contributor.authorOliveira, B.
dc.contributor.authorCafé, C.
dc.contributor.authorAlmeida, J.
dc.contributor.authorMouga, S.
dc.contributor.authorDuque, F.
dc.contributor.authorOliveira, G.
dc.contributor.authorVicente, A.M.
dc.date.accessioned2017-02-13T16:47:20Z
dc.date.available2017-11-08T01:30:14Z
dc.date.issued2016-11-07
dc.description.abstractObjective: The PARK2 gene encodes Parkin, a component of a multiprotein E3 ubiquitin ligase complex that targets substrate proteins for proteasomal degradation. PARK2 mutations are frequently associated with Parkinson’s disease, but structural alterations have also been described in patients with neurodevelopmental disorders (NDD), suggesting a pathological effect ubiquitous to neurodevelopmental and neurodegenerative brain processes. The present study aimed to define the critical regions for NDD within PARK2. Materials and methods: To clarify PARK2 involvement in NDDs, we examined the frequency and location of copy number variants (CNVs) identified in patients from our sample and reported in the literature and relevant databases, and compared with control populations. Results: Overall, the frequency of PARK2 CNVs was higher in controls than in NDD cases. However, closer inspection of the CNV location in PARK2 showed that the frequency of CNVs targeting the Parkin C-terminal, corresponding to the ring-between-ring (RBR) domain responsible for Parkin activity, is significantly higher in NDD cases than in controls. In contrast, CNVs targeting the N-terminal of Parkin, including domains that regulate ubiquitination activity, are very common both in cases and in controls. Conclusion: Although PARK2 may be a pathological factor for NDDs, likely not all variants are pathogenic, and a conclusive assessment of PARK2 variant pathogenicity requires an accurate analysis of their location within the coding region and encoded functional domains.pt_PT
dc.description.sponsorshipInês C. Conceição was supported by grant SFRH/BPD/74739/2010 from Fundação para a Ciência e Tecnologia (Portugal).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPsychiatr Genet. 2017 Apr;27(2):54-61. doi: 10.1097/YPG.0000000000000159. [Epub 2016 Nov 7]pt_PT
dc.identifier.doi10.1097/YPG.0000000000000159pt_PT
dc.identifier.issn0955-8829
dc.identifier.urihttp://hdl.handle.net/10400.18/4157
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWolters Kluwer Health, Incpt_PT
dc.relation.publisherversionhttp://insights.ovid.com/crossref?an=00041444-900000000-99607pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAutism Spectrum Disorderpt_PT
dc.subjectCopy Number Variantspt_PT
dc.subjectPARK2 genept_PT
dc.subjectParkinpt_PT
dc.subjectVariant Pathogenicitypt_PT
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mentalpt_PT
dc.titleDefinition of a putative pathological region in PARK2 associated with autism spectrum disorder through in silico analysis of its functional structurept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage8pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePsychiatric Geneticspt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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