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Molecular modelling of mitofusin 2 fora prediction for Charcot-Marie-Tooth 2A clinical severity

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dc.abstract.enCharcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant neuropathy caused by mutations in the mitofusin 2 gene (MFN2). More than 100 MFN2 gene mutations have been reported so far, with majority located within the GTPase domain encoding region. These domain-specific mutations present wide range of symptoms with differences associated with distinct amino acid substitutions in the same position. Due to the lack of conclusive phenotype-genotype correlation the predictive value of genetic results remains still limited. We have explored whether changes in the protein structure caused by MFN2 mutations can help to explain diseases phenotypes. Using a stable protein model, we evaluated the effect of 26 substitutions on the MFN2 structure and predicted the molecular consequences of such alterations. The observed changes were correlated with clinical features associated with a given mutation. Of all tested mutations positive correlation of molecular modelling with the clinical features reached 73\%. Our analysis revealed that molecular modelling of mitofusin 2 mutations is a powerful tool, which predicts associated pathogenic impacts and that these correlate with clinical outcomes. This approach may aid an early diagnosis and prediction of symptoms severity in CMT2A patients.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKochański, Andrzej
dc.contributor.authorZabłocka, Barbara
dc.contributor.authorCharzewski, Łukasz
dc.contributor.authorBeręsewicz, Małgorzata
dc.contributor.authorKrzyśko, Krystiana
dc.date.accessioned2024-01-25T12:53:26Z
dc.date.available2024-01-25T12:53:26Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.volume8
dc.identifier.doi10.1038/S41598-018-35133-9
dc.identifier.issn2045-2322
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/112871
dc.identifier.weblinkhttps://www.nature.com/articles/s41598-018-35133-9
dc.languageeng
dc.relation.ispartofScientific Reports
dc.relation.pages16900
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enNEUROPATHY TYPE 2A
dc.subject.enMITOCHONDRIAL FUSION
dc.subject.enMFN2 MUTATIONS
dc.subject.enMFN2-RELATED NEUROPATHY
dc.subject.enDISEASE TYPE-2
dc.subject.enGTP HYDROLYSIS
dc.subject.enOPTIC ATROPHY
dc.subject.enONSET
dc.subject.enPHENOTYPE
dc.subject.enPROTEIN
dc.titleMolecular modelling of mitofusin 2 fora prediction for Charcot-Marie-Tooth 2A clinical severity
dc.typeJournalArticle
dspace.entity.typePublication