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

Massimo Zollo, Mustafa Ahmed, Veronica Ferrucci, Vincenzo Salpietro, Fatemeh Asadzadeh, Marianeve Carotenuto, Reza Maroofian, Ahmed Al-Amri, Royana Singh, Iolanda Scognamiglio, Majid Mojarrad, Luca Musella, Angela Duilio, Angela Di Somma, Ender Karaca, Anna Rajab, Aisha Al-Khayat, Tribhuvan Mohan Mohapatra, Atieh Eslahi, Farah AshrafzadehLettie E. Rawlins, Rajniti Prasad, Rashmi Gupta, Preeti Kumari, Mona Srivastava, Flora Cozzolino, Sunil Kumar Rai, Maria Monti, Gaurav V. Harlalka, Michael A. Simpson, Philip Rich, Fatema Al-Salmi, Michael A. Patton, Barry A. Chioza, Stephanie Efthymiou, Francesca Granata, Gabriella Di Rosa, Sarah Wiethoff, Eugenia Borgione, Carmela Scuderi, Kshitij Mankad, Michael G. Hanna, Piero Pucci, Henry Houlden, James R. Lupski, Andrew H. Crosby, Emma L. Baple

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)940-952
Number of pages13
JournalBrain
Volume140
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Fingerprint

Microcephaly
Microtubules
Polymerization
Cell Movement
Cell Proliferation
Oman
Mutation
Brain
Human Development
Iran
Italy
India
Alleles
Neoplasms
Proteins
Neurodevelopmental Disorders

Keywords

  • Developmental delay
  • Microcephaly
  • Microtubule polymerization
  • Normal brain development
  • PRUNE1
  • Tubulinopathy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Zollo, M., Ahmed, M., Ferrucci, V., Salpietro, V., Asadzadeh, F., Carotenuto, M., ... Baple, E. L. (2017). PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. Brain, 140(4), 940-952. https://doi.org/10.1093/brain/awx014

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. / Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohapatra, Tribhuvan Mohan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E.; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Rai, Sunil Kumar; Monti, Maria; Harlalka, Gaurav V.; Simpson, Michael A.; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A.; Chioza, Barry A.; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G.; Pucci, Piero; Houlden, Henry; Lupski, James R.; Crosby, Andrew H.; Baple, Emma L.

In: Brain, Vol. 140, No. 4, 01.04.2017, p. 940-952.

Research output: Contribution to journalArticle

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, Mohapatra, TM, Eslahi, A, Ashrafzadeh, F, Rawlins, LE, Prasad, R, Gupta, R, Kumari, P, Srivastava, M, Cozzolino, F, Rai, SK, 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, vol. 140, no. 4, pp. 940-952. https://doi.org/10.1093/brain/awx014
Zollo M, Ahmed M, Ferrucci V, Salpietro V, Asadzadeh F, Carotenuto M et al. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. Brain. 2017 Apr 1;140(4):940-952. https://doi.org/10.1093/brain/awx014
Zollo, Massimo ; Ahmed, Mustafa ; Ferrucci, Veronica ; Salpietro, Vincenzo ; Asadzadeh, Fatemeh ; Carotenuto, Marianeve ; Maroofian, Reza ; Al-Amri, Ahmed ; Singh, Royana ; Scognamiglio, Iolanda ; Mojarrad, Majid ; Musella, Luca ; Duilio, Angela ; Di Somma, Angela ; Karaca, Ender ; Rajab, Anna ; Al-Khayat, Aisha ; Mohapatra, Tribhuvan Mohan ; Eslahi, Atieh ; Ashrafzadeh, Farah ; Rawlins, Lettie E. ; Prasad, Rajniti ; Gupta, Rashmi ; Kumari, Preeti ; Srivastava, Mona ; Cozzolino, Flora ; Rai, Sunil Kumar ; Monti, Maria ; Harlalka, Gaurav V. ; Simpson, Michael A. ; Rich, Philip ; Al-Salmi, Fatema ; Patton, Michael A. ; Chioza, Barry A. ; Efthymiou, Stephanie ; Granata, Francesca ; Di Rosa, Gabriella ; Wiethoff, Sarah ; Borgione, Eugenia ; Scuderi, Carmela ; Mankad, Kshitij ; Hanna, Michael G. ; Pucci, Piero ; Houlden, Henry ; Lupski, James R. ; Crosby, Andrew H. ; Baple, Emma L. / PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. In: Brain. 2017 ; Vol. 140, No. 4. pp. 940-952.
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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.",
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AU - Zollo, Massimo

AU - Ahmed, Mustafa

AU - Ferrucci, Veronica

AU - Salpietro, Vincenzo

AU - Asadzadeh, Fatemeh

AU - Carotenuto, Marianeve

AU - Maroofian, Reza

AU - Al-Amri, Ahmed

AU - Singh, Royana

AU - Scognamiglio, Iolanda

AU - Mojarrad, Majid

AU - Musella, Luca

AU - Duilio, Angela

AU - Di Somma, Angela

AU - Karaca, Ender

AU - Rajab, Anna

AU - Al-Khayat, Aisha

AU - Mohapatra, Tribhuvan Mohan

AU - Eslahi, Atieh

AU - Ashrafzadeh, Farah

AU - Rawlins, Lettie E.

AU - Prasad, Rajniti

AU - Gupta, Rashmi

AU - Kumari, Preeti

AU - Srivastava, Mona

AU - Cozzolino, Flora

AU - Rai, Sunil Kumar

AU - Monti, Maria

AU - Harlalka, Gaurav V.

AU - Simpson, Michael A.

AU - Rich, Philip

AU - Al-Salmi, Fatema

AU - Patton, Michael A.

AU - Chioza, Barry A.

AU - Efthymiou, Stephanie

AU - Granata, Francesca

AU - Di Rosa, Gabriella

AU - Wiethoff, Sarah

AU - Borgione, Eugenia

AU - Scuderi, Carmela

AU - Mankad, Kshitij

AU - Hanna, Michael G.

AU - Pucci, Piero

AU - Houlden, Henry

AU - Lupski, James R.

AU - Crosby, Andrew H.

AU - Baple, Emma L.

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KW - Tubulinopathy

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