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*

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةمراجعة النظراء

48 اقتباسات (Scopus)

ملخص

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.

اللغة الأصليةEnglish
الصفحات (من إلى)940-952
عدد الصفحات13
دوريةBrain
مستوى الصوت140
رقم الإصدار4
المعرِّفات الرقمية للأشياء
حالة النشرPublished - أبريل 1 2017

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