PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment
Zollo, M; Ahmed, M; Ferrucci, V; et al.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
Date: 28 February 2017
Journal
Brain
Publisher
Oxford University Press (OUP) for Guarantors of Brain
Publisher DOI
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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 ...
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.
Institute of Biomedical & Clinical Science
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