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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620319
Title:
PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.
Authors:
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, L E; Prasad, R; Gupta, R; Kumari, P; Srivastava, M; Cozzolino, F; Kumar Rai, S; Monti, M; Harlalka, G V; Simpson, M A; Rich, P; Al-Salmi, F; Patton, M A; Chioza, B A; Efthymiou, S; Granata, F; Di Rosa, G; Wiethoff, S; Borgione, E; Scuderi, C; Mankad, K; Hanna, M G; Pucci, P; Houlden, H; Lupski, J R; Crosby, Andrew H.; Baple, E L
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.
Citation:
PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. 2017 Brain
Publisher:
Oxford Journals
Journal:
Brain : a journal of neurology
Issue Date:
28-Feb-2017
URI:
http://hdl.handle.net/11287/620319
DOI:
10.1093/brain/awx014
PubMed ID:
28334956
Additional Links:
https://doi.org/10.1093/brain/awx014
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1460-2156
Appears in Collections:
Honorary contracts publications; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorZollo, Men
dc.contributor.authorAhmed, Men
dc.contributor.authorFerrucci, Ven
dc.contributor.authorSalpietro, Ven
dc.contributor.authorAsadzadeh, Fen
dc.contributor.authorCarotenuto, Men
dc.contributor.authorMaroofian, Ren
dc.contributor.authorAl-Amri, Aen
dc.contributor.authorSingh, Ren
dc.contributor.authorScognamiglio, Ien
dc.contributor.authorMojarrad, Men
dc.contributor.authorMusella, Len
dc.contributor.authorDuilio, Aen
dc.contributor.authorDi Somma, Aen
dc.contributor.authorKaraca, Een
dc.contributor.authorRajab, Aen
dc.contributor.authorAl-Khayat, Aen
dc.contributor.authorMohan Mohapatra, Ten
dc.contributor.authorEslahi, Aen
dc.contributor.authorAshrafzadeh, Fen
dc.contributor.authorRawlins, L Een
dc.contributor.authorPrasad, Ren
dc.contributor.authorGupta, Ren
dc.contributor.authorKumari, Pen
dc.contributor.authorSrivastava, Men
dc.contributor.authorCozzolino, Fen
dc.contributor.authorKumar Rai, Sen
dc.contributor.authorMonti, Men
dc.contributor.authorHarlalka, G Ven
dc.contributor.authorSimpson, M Aen
dc.contributor.authorRich, Pen
dc.contributor.authorAl-Salmi, Fen
dc.contributor.authorPatton, M Aen
dc.contributor.authorChioza, B Aen
dc.contributor.authorEfthymiou, Sen
dc.contributor.authorGranata, Fen
dc.contributor.authorDi Rosa, Gen
dc.contributor.authorWiethoff, Sen
dc.contributor.authorBorgione, Een
dc.contributor.authorScuderi, Cen
dc.contributor.authorMankad, Ken
dc.contributor.authorHanna, M Gen
dc.contributor.authorPucci, Pen
dc.contributor.authorHoulden, Hen
dc.contributor.authorLupski, J Ren
dc.contributor.authorCrosby, Andrew H.en
dc.contributor.authorBaple, E Len
dc.date.accessioned2017-03-24T16:24:44Z-
dc.date.available2017-03-24T16:24:44Z-
dc.date.issued2017-02-28-
dc.identifier.citationPRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. 2017 Brainen
dc.identifier.issn1460-2156-
dc.identifier.pmid28334956-
dc.identifier.doi10.1093/brain/awx014-
dc.identifier.urihttp://hdl.handle.net/11287/620319-
dc.description.abstractPRUNE 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.en
dc.language.isoenen
dc.publisherOxford Journalsen
dc.relation.urlhttps://doi.org/10.1093/brain/awx014en
dc.rightsArchived with thanks to Brain : a journal of neurologyen
dc.subjectWessex Classification Subject Headings::Neurologyen
dc.titlePRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.en
dc.typeJournal Articleen
dc.identifier.journalBrain : a journal of neurologyen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionIn press (epub ahead of print)en

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