@article {351,
	title = {Biallelic mutations in the 3{\textquoteright} exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.},
	journal = {Nat Genet},
	volume = {49},
	year = {2017},
	month = {2017 Mar},
	pages = {457-464},
	abstract = {<p>Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg-dependent 3{\textquoteright}-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo. Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3{\textquoteright} genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3{\textquoteright}-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3{\textquoteright}-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3{\textquoteright} ends.</p>},
	keywords = {Alleles, Animals, Cerebellar Diseases, Exonucleases, Female, Humans, Male, Mice, Mutation, Neurodegenerative Diseases, Nuclear Proteins, RNA, Messenger, RNA, Small Nuclear, Spliceosomes, Zebrafish},
	issn = {1546-1718},
	doi = {10.1038/ng.3762},
	author = {Lardelli, Rea M and Schaffer, Ashleigh E and Eggens, Veerle R C and Zaki, Maha S and Grainger, Stephanie and Sathe, Shashank and Van Nostrand, Eric L and Schlachetzki, Zinayida and Rosti, Basak and Akizu, Naiara and Scott, Eric and Silhavy, Jennifer L and Heckman, Laura Dean and Rosti, Rasim Ozgur and Dikoglu, Esra and Gregor, Anne and Guemez-Gamboa, Alicia and Musaev, Damir and Mande, Rohit and Widjaja, Ari and Shaw, Tim L and Markmiller, Sebastian and Marin-Valencia, Isaac and Davies, Justin H and de Meirleir, Linda and Kayserili, H{\"u}lya and Altunoglu, Umut and Freckmann, Mary Louise and Warwick, Linda and Chitayat, David and Blaser, Susan and {\c C}a{\u g}layan, Ahmet Okay and Bilguvar, Kaya and Per, H{\"u}seyin and Fagerberg, Christina and Christesen, Henrik T and Kibaek, Maria and Aldinger, Kimberly A and Manchester, David and Matsumoto, Naomichi and Muramatsu, Kazuhiro and Saitsu, Hirotomo and Shiina, Masaaki and Ogata, Kazuhiro and Foulds, Nicola and Dobyns, William B and Chi, Neil C and Traver, David and Spaccini, Luigina and Bova, Stefania Maria and Gabriel, Stacey B and G{\"u}nel, Murat and Valente, Enza Maria and Nassogne, Marie-Cecile and Bennett, Eric J and Yeo, Gene W and Baas, Frank and Lykke-Andersen, Jens and Gleeson, Joseph G}
}
@article {198,
	title = {Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.},
	journal = {J Clin Invest},
	volume = {125},
	year = {2015},
	month = {2015 Feb},
	pages = {636-51},
	abstract = {<p>Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID), abnormal extremities, and hirsutism. About 65\% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features, is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. We also identified de novo heterozygous mutations in SMC3 or SMC1A that affected RNA splicing in 2 independent patients with combined CdLS and WDSTS features. Furthermore, in families from 2 separate world populations segregating an autosomal-recessive disorder with CdLS-like features, we identified homozygous mutations in TAF6, which encodes a core transcriptional regulatory pathway component. Together, our data, along with recent transcriptome studies, suggest that CdLS and related phenotypes may be "transcriptomopathies" rather than cohesinopathies. </p>},
	keywords = {Adolescent, Adult, Cell Cycle Proteins, Child, Child, Preschool, Chondroitin Sulfate Proteoglycans, Chromosomal Proteins, Non-Histone, Codon, Nonsense, De Lange Syndrome, Exome, Exonucleases, Gene Expression Profiling, Gene Expression Regulation, Genome-Wide Association Study, Heterozygote, Histone Deacetylases, Histone-Lysine N-Methyltransferase, Humans, Infant, Male, Myeloid-Lymphoid Leukemia Protein, Phenotype, Proteins, Repressor Proteins, Transcriptome},
	issn = {1558-8238},
	doi = {10.1172/JCI77435},
	author = {Yuan, Bo and Pehlivan, Davut and Karaca, Ender and Patel, Nisha and Charng, Wu-Lin and Gambin, Tomasz and Gonzaga-Jauregui, Claudia and Sutton, V Reid and Yesil, G{\"o}zde and Bozdogan, Sevcan Tug and Tos, Tulay and Koparir, Asuman and Koparir, Erkan and Beck, Christine R and Gu, Shen and Aslan, Huseyin and Yuregir, Ozge Ozalp and Al Rubeaan, Khalid and Alnaqeb, Dhekra and Alshammari, Muneera J and Bayram, Yavuz and Atik, Mehmed M and Aydin, Hatip and Geckinli, B Bilge and Seven, Mehmet and Ulucan, Hakan and Fenercioglu, Elif and Ozen, Mustafa and Jhangiani, Shalini and Muzny, Donna M and Boerwinkle, Eric and Tuysuz, Beyhan and Alkuraya, Fowzan S and Gibbs, Richard A and Lupski, James R}
}
