@article {924,
	title = {Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly.},
	journal = {Neuron},
	volume = {109},
	year = {2021},
	month = {2021 01 20},
	pages = {241-256.e9},
	abstract = {<p>Autosomal-recessive cerebellar hypoplasia and ataxia constitute a group of heterogeneous brain disorders caused by disruption of several fundamental cellular processes. Here, we identified 10 families showing a neurodegenerative condition involving pontocerebellar hypoplasia with microcephaly (PCHM). Patients harbored biallelic mutations in genes encoding the spliceosome components Peptidyl-Prolyl Isomerase Like-1 (PPIL1) or Pre-RNA Processing-17 (PRP17). Mouse knockouts of either gene were lethal in early embryogenesis, whereas PPIL1 patient mutation knockin mice showed neuron-specific apoptosis. Loss of either protein affected splicing integrity, predominantly affecting short and high GC-content introns and genes involved in brain disorders. PPIL1 and PRP17 form an active isomerase-substrate interaction, but we found that isomerase activity is not critical for function. Thus, we establish disrupted splicing integrity and "major spliceosome-opathies" as a new mechanism underlying PCHM and neurodegeneration and uncover a non-enzymatic function of a spliceosomal proline isomerase.</p>},
	keywords = {Amino Acid Sequence, Animals, Cell Cycle Proteins, Cerebellar Diseases, Cohort Studies, Female, Gene Knockout Techniques, HEK293 Cells, Heredodegenerative Disorders, Nervous System, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microcephaly, Mutation, Pedigree, Peptidylprolyl Isomerase, Protein Structure, Secondary, Protein Structure, Tertiary, RNA Splicing Factors, Spliceosomes},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2020.10.035},
	author = {Chai, Guoliang and Webb, Alice and Li, Chen and Antaki, Danny and Lee, Sangmoon and Breuss, Martin W and Lang, Nhi and Stanley, Valentina and Anzenberg, Paula and Yang, Xiaoxu and Marshall, Trevor and Gaffney, Patrick and Wierenga, Klaas J and Chung, Brian Hon-Yin and Tsang, Mandy Ho-Yin and Pais, Lynn S and Lovgren, Alysia Kern and VanNoy, Grace E and Rehm, Heidi L and Mirzaa, Ghayda and Leon, Eyby and Diaz, Jullianne and Neumann, Alexander and Kalverda, Arnout P and Manfield, Iain W and Parry, David A and Logan, Clare V and Johnson, Colin A and Bonthron, David T and Valleley, Elizabeth M A and Issa, Mahmoud Y and Abdel-Ghafar, Sherif F and Abdel-Hamid, Mohamed S and Jennings, Patricia and Zaki, MAH S and Sheridan, Eamonn and Gleeson, Joseph G}
}
@article {355,
	title = {PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.},
	journal = {Brain},
	volume = {140},
	year = {2017},
	month = {2017 Apr 01},
	pages = {940-952},
	abstract = {<p>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.</p>},
	keywords = {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},
	issn = {1460-2156},
	doi = {10.1093/brain/awx014},
	author = {Zollo, Massimo and Ahmed, Mustafa and Ferrucci, Veronica and Salpietro, Vincenzo and Asadzadeh, Fatemeh and Carotenuto, Marianeve and Maroofian, Reza and Al-Amri, Ahmed and Singh, Royana and Scognamiglio, Iolanda and Mojarrad, Majid and Musella, Luca and Duilio, Angela and Di Somma, Angela and Karaca, Ender and Rajab, Anna and Al-Khayat, Aisha and Mohan Mohapatra, Tribhuvan and Eslahi, Atieh and Ashrafzadeh, Farah and Rawlins, Lettie E and Prasad, Rajniti and Gupta, Rashmi and Kumari, Preeti and Srivastava, Mona and Cozzolino, Flora and Kumar Rai, Sunil and Monti, Maria and Harlalka, Gaurav V and Simpson, Michael A and Rich, Philip and Al-Salmi, Fatema and Patton, Michael A and Chioza, Barry A and Efthymiou, Stephanie and Granata, Francesca and Di Rosa, Gabriella and Wiethoff, Sarah and Borgione, Eugenia and Scuderi, Carmela and Mankad, Kshitij and Hanna, Michael G and Pucci, Piero and Houlden, Henry and Lupski, James R and Crosby, Andrew H and Baple, Emma L}
}
