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Article: Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome

TitleCirculating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome
Authors
KeywordsMECP2 mutation
natural history
neurological disease
neuroprostanes
phenotype
Issue Date2021
PublisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
Citation
International Journal of Molecular Sciences, 2021, v. 22 n. 8, p. article no. 4240 How to Cite?
AbstractNeuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between MECP2 mutations or RTT disease progression and plasma levels of 4(RS)-4-F4t-neuroprostane (4-F4t-NeuroP) and 10(RS)-10-F4t-neuroprostane (10-F4t-NeuroP) in typical RTT patients with proven MECP2 gene mutation. Clinical severity and disease progression were assessed using the Rett clinical severity scale (RCSS) in n = 77 RTT patients. The 4-F4t-NeuroP and 10-F4t-NeuroP molecules were totally synthesized and used to identify the contents of the plasma of the patients. Neuroprostane levels were related to MECP2 mutation category (i.e., early truncating, gene deletion, late truncating, and missense), specific hotspot mutations (i.e., R106W, R133C, R168X, R255X, R270X, R294X, R306C, and T158M), and disease stage (II through IV). Circulating 4-F4t-NeuroP and 10-F4t-NeuroP were significantly related to (i) the type of MECP2 mutations where higher levels were associated to gene deletions (p ≤ 0.001); (ii) severity of common hotspot MECP2 mutation (large deletions, R168X, R255X, and R270X); (iii) disease stage, where higher concentrations were observed at stage II (p ≤ 0.002); and (iv) deficiency in walking (p ≤ 0.0003). This study indicates the biological significance of 4-F4t-NeuroP and 10-F4t-NeuroP as promising molecules to mark the disease progression and potentially gauge genotype–phenotype associations in RTT.
Persistent Identifierhttp://hdl.handle.net/10722/299331
ISSN
2020 Impact Factor: 5.923
2020 SCImago Journal Rankings: 1.455
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSignorini, C-
dc.contributor.authorLeoncini, S-
dc.contributor.authorDurand, T-
dc.contributor.authorGalano, JM-
dc.contributor.authorGuy, A-
dc.contributor.authorBultel-Poncé, V-
dc.contributor.authorOger, C-
dc.contributor.authorLee, JCY-
dc.contributor.authorCiccoli, L-
dc.contributor.authorHayek, J-
dc.contributor.authorDe Felice, C-
dc.date.accessioned2021-05-10T07:00:16Z-
dc.date.available2021-05-10T07:00:16Z-
dc.date.issued2021-
dc.identifier.citationInternational Journal of Molecular Sciences, 2021, v. 22 n. 8, p. article no. 4240-
dc.identifier.issn1661-6596-
dc.identifier.urihttp://hdl.handle.net/10722/299331-
dc.description.abstractNeuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between MECP2 mutations or RTT disease progression and plasma levels of 4(RS)-4-F4t-neuroprostane (4-F4t-NeuroP) and 10(RS)-10-F4t-neuroprostane (10-F4t-NeuroP) in typical RTT patients with proven MECP2 gene mutation. Clinical severity and disease progression were assessed using the Rett clinical severity scale (RCSS) in n = 77 RTT patients. The 4-F4t-NeuroP and 10-F4t-NeuroP molecules were totally synthesized and used to identify the contents of the plasma of the patients. Neuroprostane levels were related to MECP2 mutation category (i.e., early truncating, gene deletion, late truncating, and missense), specific hotspot mutations (i.e., R106W, R133C, R168X, R255X, R270X, R294X, R306C, and T158M), and disease stage (II through IV). Circulating 4-F4t-NeuroP and 10-F4t-NeuroP were significantly related to (i) the type of MECP2 mutations where higher levels were associated to gene deletions (p ≤ 0.001); (ii) severity of common hotspot MECP2 mutation (large deletions, R168X, R255X, and R270X); (iii) disease stage, where higher concentrations were observed at stage II (p ≤ 0.002); and (iv) deficiency in walking (p ≤ 0.0003). This study indicates the biological significance of 4-F4t-NeuroP and 10-F4t-NeuroP as promising molecules to mark the disease progression and potentially gauge genotype–phenotype associations in RTT.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms-
dc.relation.ispartofInternational Journal of Molecular Sciences-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMECP2 mutation-
dc.subjectnatural history-
dc.subjectneurological disease-
dc.subjectneuroprostanes-
dc.subjectphenotype-
dc.titleCirculating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome-
dc.typeArticle-
dc.identifier.emailLee, JCY: jettylee@hku.hk-
dc.identifier.authorityLee, JCY=rp01511-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/ijms22084240-
dc.identifier.pmid33921863-
dc.identifier.pmcidPMC8073126-
dc.identifier.scopuseid_2-s2.0-85104464492-
dc.identifier.hkuros322378-
dc.identifier.volume22-
dc.identifier.issue8-
dc.identifier.spagearticle no. 4240-
dc.identifier.epagearticle no. 4240-
dc.identifier.isiWOS:000644345100001-
dc.publisher.placeSwitzerland-

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