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PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

Zollo, M; Ahmed, M; Ferrucci, V; Salpietro, V; Asadzadeh, F; Carotenuto, M; Maroofian, R; Al-Amri, A; Singh, R; Scognamiglio, I; et al. Zollo, M; Ahmed, M; Ferrucci, V; Salpietro, V; Asadzadeh, F; Carotenuto, M; Maroofian, R; Al-Amri, A; Singh, R; Scognamiglio, I; Mojarrad, M; Musella, L; Duilio, A; Di Somma, A; Karaca, E; Rajab, A; Al-Khayat, A; Mohan Mohapatra, T; Eslahi, A; Ashrafzadeh, F; Rawlins, LE; Prasad, R; Gupta, R; Kumari, P; Srivastava, M; Cozzolino, F; Kumar Rai, S; Monti, M; Harlalka, GV; Simpson, MA; Rich, P; Al-Salmi, F; Patton, MA; Chioza, BA; Efthymiou, S; Granata, F; Di Rosa, G; Wiethoff, S; Borgione, E; Scuderi, C; Mankad, K; Hanna, MG; Pucci, P; Houlden, H; Lupski, JR; Crosby, AH; Baple, EL (2017) PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. Brain, 140 (4). pp. 940-952. ISSN 1460-2156 https://doi.org/10.1093/brain/awx014
SGUL Authors: Patton, Michael Alexander

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Abstract

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.

Item Type: Article
Additional Information: © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: PRUNE1, developmental delay, microcephaly, microtubule polymerization, tubulinopathy, normal brain development, Adolescent, Brain, Carrier Proteins, Cell Differentiation, Cell Movement, Cerebral Cortex, Child, Child, Preschool, Cytoskeleton, Developmental Disabilities, Female, Genes, Recessive, Heredodegenerative Disorders, Nervous System, Humans, Infant, Male, Microcephaly, Microtubules, Mutation, Pedigree, Young Adult, PRUNE1, microcephaly, developmental delay, normal brain development, microtubule polymerization, tubulinopathy, Neurology & Neurosurgery, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Journal or Publication Title: Brain
ISSN: 1460-2156
Language: eng
Dates:
DateEvent
1 April 2017Published
28 February 2017Published Online
13 December 2016Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
WT093205 MAWellcome Trusthttp://dx.doi.org/10.13039/100004440
WT104033AIAWellcome Trusthttp://dx.doi.org/10.13039/100004440
WT098051Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 28334956
Web of Science ID: WOS:000397319400018
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108821
Publisher's version: https://doi.org/10.1093/brain/awx014

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