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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

1
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy;[email protected]
2
Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy;[email protected]
3
Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy;[email protected]
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Institut des Biomolécules Max Mousseron, (IBMM), UMR 5247, CNRS, Université de Montpellier, ENSCM, CEDEX 5, 34093 Montpellier, France
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School of Biological Sciences, The University of Hong Kong, Hong Kong
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Pediatric Speciality Center “L’Isola di Bau”, 50052 Certaldo, Florence, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Michele Papa
Int. J. Mol. Sci. 2021, 22(8), 4240; https://doi.org/10.3390/ijms22084240
Received: 16 March 2021 / Revised: 10 April 2021 / Accepted: 15 April 2021 / Published: 19 April 2021
Neuroprostanes, 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. View Full-Text
Keywords: MECP2 mutation; natural history; neurological disease; neuroprostanes; phenotype; Rett syndrome MECP2 mutation; natural history; neurological disease; neuroprostanes; phenotype; Rett syndrome
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MDPI and ACS Style

Signorini, C.; Leoncini, S.; Durand, T.; Galano, J.-M.; Guy, A.; Bultel-Poncé, V.; Oger, C.; Lee, J.C.-Y.; Ciccoli, L.; Hayek, J.; De Felice, C. Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome. Int. J. Mol. Sci. 2021, 22, 4240. https://doi.org/10.3390/ijms22084240

AMA Style

Signorini C, Leoncini S, Durand T, Galano J-M, Guy A, Bultel-Poncé V, Oger C, Lee JC-Y, Ciccoli L, Hayek J, De Felice C. Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome. International Journal of Molecular Sciences. 2021; 22(8):4240. https://doi.org/10.3390/ijms22084240

Chicago/Turabian Style

Signorini, Cinzia, Silvia Leoncini, Thierry Durand, Jean-Marie Galano, Alexandre Guy, Valérie Bultel-Poncé, Camille Oger, Jetty C.-Y. Lee, Lucia Ciccoli, Joussef Hayek, and Claudio De Felice. 2021. "Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome" International Journal of Molecular Sciences 22, no. 8: 4240. https://doi.org/10.3390/ijms22084240

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