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181 results on '"Yasuno, Katsuhito"'

1. Dysregulation of mTOR signalling is a converging mechanism in lissencephaly

Author

Zhang, Ce, Liang, Dan, Ercan-Sencicek, A. Gulhan, Bulut, Aybike S., Cortes, Joelly, Cheng, Iris Q., Henegariu, Octavian, Nishimura, Sayoko, Wang, Xinyuan, Peksen, A. Buket, Takeo, Yutaka, Caglar, Caner, Lam, TuKiet T., Koroglu, Merve Nur, Narayanan, Anand, Lopez-Giraldez, Francesc, Miyagishima, Danielle F., Mishra-Gorur, Ketu, Barak, Tanyeri, Yasuno, Katsuhito, Erson-Omay, E. Zeynep, Yalcinkaya, Cengiz, Wang, Guilin, Mane, Shrikant, Kaymakcalan, Hande, Guzel, Aslan, Caglayan, A. Okay, Tuysuz, Beyhan, Sestan, Nenad, Gunel, Murat, Louvi, Angeliki, and Bilguvar, Kaya

Published
2025
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2. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas

Author

Youngblood, Mark W., Erson-Omay, Zeynep, Li, Chang, Najem, Hinda, Coșkun, Süleyman, Tyrtova, Evgeniya, Montejo, Julio D., Miyagishima, Danielle F., Barak, Tanyeri, Nishimura, Sayoko, Harmancı, Akdes Serin, Clark, Victoria E., Duran, Daniel, Huttner, Anita, Avşar, Timuçin, Bayri, Yasar, Schramm, Johannes, Boetto, Julien, Peyre, Matthieu, Riche, Maximilien, Goldbrunner, Roland, Amankulor, Nduka, Louvi, Angeliki, Bilgüvar, Kaya, Pamir, M. Necmettin, Özduman, Koray, Kilic, Türker, Knight, James R., Simon, Matthias, Horbinski, Craig, Kalamarides, Michel, Timmer, Marco, Heimberger, Amy B., Mishra-Gorur, Ketu, Moliterno, Jennifer, Yasuno, Katsuhito, and Günel, Murat

Published
2023
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3. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans

Author

Barak, Tanyeri, Ristori, Emma, Ercan-Sencicek, A. Gulhan, Miyagishima, Danielle F., Nelson-Williams, Carol, Dong, Weilai, Jin, Sheng Chih, Prendergast, Andrew, Armero, William, Henegariu, Octavian, Erson-Omay, E. Zeynep, Harmancı, Akdes Serin, Guy, Mikhael, Gültekin, Batur, Kilic, Deniz, Rai, Devendra K., Goc, Nükte, Aguilera, Stephanie Marie, Gülez, Burcu, Altinok, Selin, Ozcan, Kent, Yarman, Yanki, Coskun, Süleyman, Sempou, Emily, Deniz, Engin, Hintzen, Jared, Cox, Andrew, Fomchenko, Elena, Jung, Su Woong, Ozturk, Ali Kemal, Louvi, Angeliki, Bilgüvar, Kaya, Connolly, Jr., E. Sander, Khokha, Mustafa K., Kahle, Kristopher T., Yasuno, Katsuhito, Lifton, Richard P., Mishra-Gorur, Ketu, Nicoli, Stefania, and Günel, Murat

Published
2021
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6. Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly

Author

Li, Hongda, Bielas, Stephanie L, Zaki, Maha S, Ismail, Samira, Farfara, Dorit, Um, Kyongmi, Rosti, Rasim O, Scott, Eric C, Tu, Shu, Chi, Neil C, Gabriel, Stacey, Erson-Omay, Emine Z, Ercan-Sencicek, A Gulhan, Yasuno, Katsuhito, Çağlayan, Ahmet Okay, Kaymakçalan, Hande, Ekici, Barış, Bilguvar, Kaya, Gunel, Murat, and Gleeson, Joseph G

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Brain Disorders, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Rare Diseases, Pediatric, Stem Cell Research, Intellectual and Developmental Disabilities (IDD), Stem Cell Research - Induced Pluripotent Stem Cell, Congenital Structural Anomalies, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alleles, Apoptosis, Centrosome, Child, Child, Preschool, Cytokinesis, Female, Genes, Recessive, Humans, Infant, Newborn, Intracellular Signaling Peptides and Proteins, Male, Microcephaly, Mitosis, Mutation, Missense, Pedigree, Protein Serine-Threonine Kinases, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Cell division terminates with cytokinesis and cellular separation. Autosomal-recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by a reduction in brain and head size at birth in addition to non-progressive intellectual disability. MCPH is genetically heterogeneous, and 16 loci are known to be associated with loss-of-function mutations predominantly affecting centrosomal-associated proteins, but the multiple roles of centrosomes in cellular function has left questions about etiology. Here, we identified three families affected by homozygous missense mutations in CIT, encoding citron rho-interacting kinase (CIT), which has established roles in cytokinesis. All mutations caused substitution of conserved amino acid residues in the kinase domain and impaired kinase activity. Neural progenitors that were differentiated from induced pluripotent stem cells (iPSCs) derived from individuals with these mutations exhibited abnormal cytokinesis with delayed mitosis, multipolar spindles, and increased apoptosis, rescued by CRISPR/Cas9 genome editing. Our results highlight the importance of cytokinesis in the pathology of primary microcephaly.

Published
2016

7. CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration

Author

Schaffer, Ashleigh E, Eggens, Veerle RC, Caglayan, Ahmet Okay, Reuter, Miriam S, Scott, Eric, Coufal, Nicole G, Silhavy, Jennifer L, Xue, Yuanchao, Kayserili, Hulya, Yasuno, Katsuhito, Rosti, Rasim Ozgur, Abdellateef, Mostafa, Caglar, Caner, Kasher, Paul R, Cazemier, J Leonie, Weterman, Marian A, Cantagrel, Vincent, Cai, Na, Zweier, Christiane, Altunoglu, Umut, Satkin, N Bilge, Aktar, Fesih, Tuysuz, Beyhan, Yalcinkaya, Cengiz, Caksen, Huseyin, Bilguvar, Kaya, Fu, Xiang-Dong, Trotta, Christopher R, Gabriel, Stacey, Reis, André, Gunel, Murat, Baas, Frank, and Gleeson, Joseph G

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Neurodegenerative, Genetics, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Neurological, Animals, Brain, Cerebellum, Cleavage And Polyadenylation Specificity Factor, Female, Humans, Male, Mice, Models, Molecular, Neurodegenerative Diseases, Nuclear Proteins, Pedigree, Phosphotransferases, RNA Splicing, RNA, Transfer, Saccharomyces cerevisiae, Transcription Factors, Zebrafish, Zebrafish Proteins, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.

Published
2014

9. OMICS AND PROGNSTIC MARKERS

Author

Larson, Peder, Yoshihara, Hikari, Vigneron, Daniel, Nelson, Sarah, Pieper, Russell, Phillips, Joanna, Ronen, Sabrina, Clark, Victoria, Omay, Zeynep, Serin, Akdes, Günel, Jennifer, Omay, Bulent, Grady, Conor, Youngblood, Mark, Bilgüvar, Kaya, Baehring, Joachim, Piepmeier, Joseph, Gutin, Philip, Vortmeyer, Alexander, Brennan, Cameron, Pamir, M, Kilic, Türker, Krischek, Boris, Simon, Matthias, Yasuno, Katsuhito, Günel, Murat, Cohen, Adam, Sato, Mariko, Aldape, Kenneth, Mason, Clint, Diefes, Kristen, Heathcock, Lindsey, Abegglen, Lisa, Shrieve, Dennis, Couldwell, William, Schiffman, Joshua, Colman, Howard, DAlessandris, Quintino, Cenci, Tonia, Martini, Maurizio, Ricci-Vitiani, Lucia, De Maria, Ruggero, Larocca, Luigi, Pallini, Roberto, de Groot, John, Theeler, Brett, Lang, Frederick, Rao, Ganesh, Gilbert, Mark, Sulman, Erik, Luthra, Raja, Eterovic, Karina, Chen, Ken, Routbort, Mark, Verhaak, Roeland, Mills, Gordon, Mendelsohn, John, Meric-Bernstam, Funda, Yung, Alfred, Fujii, Kentaro, Kurozumi, Kazuhiko, Ichikawa, Tomotsugu, Onishi, Manabu, Ishida, Joji, Shimazu, Yosuke, Kaur, Balveen, Chiocca, E, Date, Isao, Geisenberger, Christoph, Mock, Andreas, Warta, Rolf, Schwager, Christian, Hartmann, Christian, von Deimling, Andreas, Abdollahi, Amir, Herold-Mende, Christel, Gevaert, Olivier, Achrol, Achal, Gholamin, Sharareh, Mitra, Siddhartha, Westbroek, Erick, Loya, Joshua, Mitchell, Lex, Chang, Steven, Steinberg, Gary, Plevritis, Sylvia, Cheshier, Samuel, Xu, Jiajing, Napel, Sandy, and Zaharchuk, Greg

Abstract

Although histopathological diagnosis is essential in decision of therapeutic strategy for gliomas, sometimes the tumors diagnosed in one histological entity show thoroughly different clinical courses. This phenomenon is believed to be due primarily to the presence of the genetic subgroup. In fact, relationship between treatment response and certain genetic characteristics is indicated (e.g. better chemosensitivity in glioma with losses of 1p/19q (−1p/19q)). It is highly likely that genetic classification of glioma is useful to select the adjuvant treatment. Additionally, gain of 7q (+7q) and −1p/19q are early events in 2 distinct tumor lineages, astrocytic tumors and oligodendroglial tumors, respectively, and these tumors obtain additional genetic aberration (−9p, 10q) with tumor progression. On the other hand, concerning the tumors without +7q or −1p/19q, little is known about clinically important genetic aberration. Therefore the study on such tumors could provide useful information for the prognosis prediction and the determination of treatment strategy. METHODS: We selected 39 cases of gliomas without +7q or −1p/19q from 200 adult supratentorial glioma cases surgically treated and analyzed chromosomal DNA copy number aberrations (CNAs) by comparative genomic hybridization (CGH) from 2005 to 2012. We correlated clinical features of these tumors with histological characteristics, CNAs and IDH1 status. RESULTS: The clinical course of gliomas without +7q or −1p/19q was not correlated with additional genetic aberration of -9p or 10q, which have been known as genetic markers for poor prognosis, and absence of +7q or −1p/19q was maintained at the time of recurrence. The tumors without +7q or −1p/19q showed relatively favorable prognosis although mutation of IDH1 was infrequent in these tumors (35.8 %). CONCLUSION: The gliomas without +7q or −1p/19q have clinical features distinct from the +7q and −1p/19q gliomas. Prognostic markers for each subgroups could help establish therapeutic strategy against the tumor. DNA methylation is a mechanism altering the normal state of cells implicated in many cancers. Currently the methylation status of MGMT is one of the most widely utilized clinical genetic tests performed on glioblastoma multiforme (GBM). While several global gene expression signatures have been developed, it is unclear if genome-wide DNA methylation signatures can predict prognosis in cancer. We used a computational algorithm (MethylMix) to analyze genome-wide DNA methylation in GBM data obtained from The Cancer Genome Atlas (TCGA). MethylMix identified a set of driver genes that met criteria for being both differential and functional. Differential refers to a difference in cancer methylation compared to normal tissue; functional refers to having a significant correlation with matched gene expression changes. We then used these MethylMix driver genes to build multivariate models of overall survival using linear regression and validated these models in independent data sets. Applying MethylMix and linear regression we identified a novel methylation signature predictive of overall survival, which we here define as the GLIOMETH signature. Interestingly, GLIOMETH did not include MGMT, suggesting that MGMT methylation is not essential to predict prognosis in GBM. GLIOMETH was prognostically significant even in a multivariate analysis with known prognostic covariates, including MGMT methylation. We validated GLIOMETH in two external DNA methylation data sets and two gene expression data sets, using a leveraging technique predicting methylation in terms of gene expression, showing also a significant survival correlation. Differential and functional DNA methylation is predictive of overall survival in GBM independent of known prognostic factors. We identified GLIOMETH as a DNA methylation signature that is predictive of overall survival in GBM, outperforming MGMT methylation. The GLIOMETH model validated across multiple independent DNA methylation and gene expression validation data sets demonstrating its robustness as an independent predictor of prognosis in GBM. Recent next-generation genomic studies of medulloblastoma have revealed an unexpected and overwhelming convergence of somatic alterations affecting chromatin-modifying genes. Estimates informed by next-generation sequencing implicate that at least one third of all medulloblastomas have somatic mutations in a chromatin modifier, including those targeting histone methyltransfereses, histone demethylases, and related chromatin modulators that collectively function to influence chromatin conformation associated gene expression states. These mutations occur across all four medulloblastoma subgroups although different sets of genes appear to be selectively altered in a subgroup-specific manner. Despite the abundance of evidence implicating deregulation of chromatin modifiers as a key event in medulloblastoma pathogenesis, the medulloblastoma epigenome remains largely unexplored, and studies cataloguing histone modification states on a genome-wide scale have yet to be reported. To comprehensively investigate the histone code in medulloblastoma and the consequences associated with mutations affecting histone-modifying genes, we have performed ChIP-sequencing on a set of well-characterized primary medulloblastoma specimens. Histone marks examined in this study include the six modifications mandated by the International Human Epigenome Consortium (IHEC), including H3K4me3, H3K9me3, H3K27me3, H3K27ac, H3K4me1 and H3K36me3. Chromatin isolates from primary fresh-frozen tissues representative of each medulloblastoma subgroup were immunoprecipitated with the indicated antibodies and sequenced with a HiSeq Illumina sequencer to obtain at least 10 million unique reads per ChIP experiment. Peak calling was performed using multiple publicly available tools and data integrated with existing ENCODE data for the same histone marks. Inter-subgroup comparisons of histone modification states revealed a wealth of distinguishing genomic regions that were highly correlated with alternative patterns of gene expression existing between the subgroups. Moreover, integration with existing mutational profiles demonstrated aberrant chromatin states that could be linked to underlying mutations in select chromatin modifiers. Ongoing work will focus on expanding the cohort and integration with all levels of ‘omic data.

Published
2013

10. Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO

Author

Clark, Victoria E, Erson-Omay, E Zeynep, Serin, Akdes, Yin, Jun, Cotney, Justin, Özduman, Koray, Avşar, Timuçin, Li, Jie, Murray, Phillip B, Henegariu, Octavian, Yilmaz, Saliha, Günel, Jennifer Moliterno, Carrión-Grant, Geneive, Yılmaz, Baran, Grady, Conor, Tanrıkulu, Bahattin, Bakırcıoğlu, Mehmet, Kaymakçalan, Hande, Caglayan, Ahmet Okay, Sencar, Leman, Ceyhun, Emre, Atik, A Fatih, Bayri, Yaşar, Bai, Hanwen, Kolb, Luis E, Hebert, Ryan M, Omay, S Bulent, Mishra-Gorur, Ketu, Choi, Murim, Overton, John D, Holland, Eric C, Mane, Shrikant, State, Matthew W, Bilgüvar, Kaya, Baehring, Joachim M, Gutin, Philip H, Piepmeier, Joseph M, Vortmeyer, Alexander, Brennan, Cameron W, Pamir, M Necmettin, Kılıç, Türker, Lifton, Richard P, Noonan, James P, Yasuno, Katsuhito, and Günel, Murat

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Brain Disorders, Rare Diseases, Brain Cancer, Neurosciences, Human Genome, Cancer, Adult, Aged, Aged, 80 and over, Brain Neoplasms, Chromosomes, Human, Pair 22, DNA Mutational Analysis, Female, Genes, Neurofibromatosis 2, Genomic Instability, Genomics, Humans, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors, Male, Meningeal Neoplasms, Meningioma, Middle Aged, Mutation, Neoplasm Grading, Proto-Oncogene Proteins c-akt, Receptors, G-Protein-Coupled, Smoothened Receptor, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, General Science & Technology
Abstract

We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.

Published
2013

11. Perturbations of Spatially Closed Bianchi III Spacetimes

Author

Tanimoto, Masayuki, Moncrief, Vincent, and Yasuno, Katsuhito

Subjects
General Relativity and Quantum Cosmology
Abstract

Motivated by the recent interest in dynamical properties of topologically nontrivial spacetimes, we study linear perturbations of spatially closed Bianchi III vacuum spacetimes, whose spatial topology is the direct product of a higher genus surface and the circle. We first develop necessary mode functions, vectors, and tensors, and then perform separations of (perturbation) variables. The perturbation equations decouple in a way that is similar to but a generalization of those of the Regge--Wheeler spherically symmetric case. We further achieve a decoupling of each set of perturbation equations into gauge-dependent and independent parts, by which we obtain wave equations for the gauge-invariant variables. We then discuss choices of gauge and stability properties. Details of the compactification of Bianchi III manifolds and spacetimes are presented in an appendix. In the other appendices we study scalar field and electromagnetic equations on the same background to compare asymptotic properties., Comment: 61 pages, 1 figure, final version with minor corrections, to appear in Class. Quant. Gravit

Published
2002
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12. Thurston's Geometrization Conjecture and cosmological models

Author

Yasuno, Katsuhito, Koike, Tatsuhiko, and Siino, Masaru

Subjects
General Relativity and Quantum Cosmology
Abstract

We investigate a class of spatially compact inhomogeneous spacetimes. Motivated by Thurston's Geometrization Conjecture, we give a formulation for constructing spatially compact composite spacetimes as solutions for the Einstein equations. Such composite spacetimes are built from the spatially compact locally homogeneous vacuum spacetimes which have two commuting Killing vectors by gluing them through a timelike hypersurface admitting a homogeneous spatial slice spanned by the commuting Killing vectors. Topology of the spatial section of the timelike boundary is taken to be the torus. We also assume that the matter which will arise from the gluing is compressed on the boundary, i.e. we take the thin-shell approximation. By solving the junction conditions, we can see dynamical behavior of the connected (composite) spacetime. The Teichm\"uller deformation of the torus also can be obtained. We apply our formalism to a concrete model. The relation to the torus sum of 3-manifolds and the difficulty of this problem are also discussed., Comment: 18 pages, no figures, LaTex 2e, IOP style, Submitted to Class. Quantum Grav

Published
2000
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13. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.

Author

Bilgüvar, Kaya, Oztürk, Ali Kemal, Louvi, Angeliki, Kwan, Kenneth Y, Choi, Murim, Tatli, Burak, Yalnizoğlu, Dilek, Tüysüz, Beyhan, Cağlayan, Ahmet Okay, Gökben, Sarenur, Kaymakçalan, Hande, Barak, Tanyeri, Bakircioğlu, Mehmet, Yasuno, Katsuhito, Ho, Winson, Sanders, Stephan, Zhu, Ying, Yilmaz, Sanem, Dinçer, Alp, Johnson, Michele H, Bronen, Richard A, Koçer, Naci, Per, Hüseyin, Mane, Shrikant, Pamir, Mehmet Necmettin, Yalçinkaya, Cengiz, Kumandaş, Sefer, Topçu, Meral, Ozmen, Meral, Sestan, Nenad, Lifton, Richard P, State, Matthew W, and Günel, Murat

Subjects
Brain, Animals, Humans, Mice, Microcephaly, Brain Diseases, Nerve Tissue Proteins, Pedigree, DNA Mutational Analysis, Base Sequence, Genes, Recessive, Mutation, Molecular Sequence Data, Female, Male, Genes, Recessive, General Science & Technology
Abstract

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.

Published
2010

14. Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors

Author

Mishra-Gorur, Ketu, Çağlayan, Ahmet Okay, Schaffer, Ashleigh E., Chabu, Chiswili, Henegariu, Octavian, Vonhoff, Fernando, Akgümüş, Gözde Tuğce, Nishimura, Sayoko, Han, Wenqi, Tu, Shu, Baran, Burçin, Gümüş, Hakan, Dilber, Cengiz, Zaki, Maha S., Hossni, Heba A.A., Rivière, Jean-Baptiste, Kayserili, Hülya, Spencer, Emily G., Rosti, Rasim Ö., Schroth, Jana, Per, Hüseyin, Çağlar, Caner, Çağlar, Çağri, Dölen, Duygu, Baranoski, Jacob F., Kumandaş, Sefer, Minja, Frank J., Erson-Omay, E. Zeynep, Mane, Shrikant M., Lifton, Richard P., Xu, Tian, Keshishian, Haig, Dobyns, William B., Chi, Neil C., Šestan, Nenad, Louvi, Angeliki, Bilgüvar, Kaya, Yasuno, Katsuhito, Gleeson, Joseph G., and Günel, Murat

Published
2014
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15. Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

Author

Caglayan, Ahmet Okay, Baranoski, Jacob F., Aktar, Fesih, Han, Wengi, Tuysuz, Beyhan, Guzel, Aslan, Guclu, Bulent, Kaymakcalan, Hande, Aktekin, Berrin, Akgumus, Gozde Tugce, Murray, Phillip B., Erson-Omay, Emine Z., Caglar, Caner, Bakircioglu, Mehmet, Sakalar, Yildirim Bayezit, Guzel, Ebru, Demir, Nihat, Tuncer, Oguz, Senturk, Senem, Ekici, Baris, Minja, Frank J., Šestan, Nenad, Yasuno, Katsuhito, Bilguvar, Kaya, Caksen, Huseyin, and Gunel, Murat

Published
2014
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16. Correction: Author Correction: Integrated genomic analyses of de novo pathways underlying atypical meningiomas

Author

Harmancı, Akdes Serin, Youngblood, Mark W., Clark, Victoria E., Coşkun, Süleyman, Henegariu, Octavian, Duran, Daniel, Erson-Omay, E. Zeynep, Kaulen, Leon D., Lee, Tong Ihn, Abraham, Brian J., Simon, Matthias, Krischek, Boris, Timmer, Marco, Goldbrunner, Roland, Omay, S. Bülent, Baranoski, Jacob, Baran, Burçin, Carrión-Grant, Geneive, Bai, Hanwen, Mishra-Gorur, Ketu, Schramm, Johannes, Moliterno, Jennifer, Vortmeyer, Alexander O., Bilgüvar, Kaya, Yasuno, Katsuhito, Young, Richard A., and Günel, Murat

Published
2018
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18. Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism

Author

Fernandez, Thomas V., Sanders, Stephan J., Yurkiewicz, Ilana R., Ercan-Sencicek, A. Gulhan, Kim, Young-Shin, Fishman, Daniel O., Raubeson, Melanie J., Song, Youeun, Yasuno, Katsuhito, Ho, Winson S.C., Bilguvar, Kaya, Glessner, Joseph, Chu, Su Hee, Leckman, James F., King, Robert A., Gilbert, Donald L., Heiman, Gary A., Tischfield, Jay A., Hoekstra, Pieter J., Devlin, Bernie, Hakonarson, Hakon, Mane, Shrikant M., Günel, Murat, and State, Matthew W.

Published
2012
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19. Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk

Author

Yasuno, Katsuhito, Bakırcıoğlu, Mehmet, Low, Siew-Kee, Bilgüvar, Kaya, Gaál, Emília, Ruigrok, Ynte M., Niemelä, Mika, Hata, Akira, Bijlenga, Philippe, Kasuya, Hidetoshi, Jääskeläinen, Juha E., Krex, Dietmar, Auburger, Georg, Simon, Matthias, Krischek, Boris, Ozturk, Ali K., Mane, Shrikant, Rinkel, Gabriel J. E., Steinmetz, Helmuth, Hernesniemi, Juha, Schaller, Karl, Zembutsu, Hitoshi, Inoue, Ituro, Palotie, Aarno, Cambien, François, Nakamura, Yusuke, Lifton, Richard P., and Günel, Murat

Published
2011

21. L-histidine decarboxylase and Tourette's syndrome

Author

Ercan-Sencicek, A. Gulhan, Stillman, Althea A., Ghosh, Ananda K., Bilguvar, Kaya, O'Roak, Brian J., Mason, Christopher E., Abbott, Thomas, Gupta, Abha, King, Robert A., Pauls, David L., Tischfield, Jay A., Heiman, Gary A., Singer, Harvey S., Gilbert, Donald L., Hoekstra, Pieter J., Morgan, Thomas M., Loring, Erin, Yasuno, Katsuhito, Fernandez, Thomas, Sanders, Stephan, Louvi, Angeliki, Cho, Judy H., Mane, Shrikant, Colangelo, Christopher M., Biederer, Thomas, Lifton, Richard P., Gunel, Murat, and State, Matthew W.

Subjects
Decarboxylases -- Genetic aspects, Gene mutations -- Analysis, Histidine -- Research, Tourette's syndrome -- Genetic aspects, Tourette's syndrome -- Diagnosis, Tourette's syndrome -- Care and treatment
Abstract

An analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase and Tourette's syndrome, the rate-limiting enzyme in histamine biosynthesis is described. The study findings along with the published data from model system provide insight into the role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics.

Published
2010

23. Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism

Author

Makino, Satoshi, Kaji, Ryuji, Ando, Satoshi, Tomizawa, Maiko, Yasuno, Katsuhito, Goto, Satoshi, Matsumoto, Shinnichi, Tabuena, Ma Daisy, Maranon, Elma, Dantes Marita, Lee, Lillian V., Ogasawara, Kazumasa, Tooyama, Ikuo, Akatsu, Hiroyasu, Nishimura, Masataka, and Tamiya, Gen

Subjects
Dystonia -- Research, Parkinsonism -- Genetic aspects, Parkinsonism -- Research, DNA binding proteins -- Structure, DNA binding proteins -- Research, Dopamine receptors -- Research, Biological sciences
Abstract

Various studies are performed to reveal the disease-causative gene of X-linked dystonia-parkinsonism (XDP). The genome sequencing analysis and expression analysis have shown that the reduced neuron-specific expression of the TATA-binding protein-associated factor 1 gene (TAF1) is associated with XDP.

Published
2007

25. Contributors

Author

Aarabi, Bizhan, Abbott, Rick, Abd-El-Barr, Muhammad M., Abel, Taylor J., Abou-Al-Shaar, Hussam, Acar, Feridun, Achey, Rebecca L., Ackerman, Laurie L., Adappa, Nithin D., Adelson, P. David, Agarwal, Nitin, Aguirre-Padilla, David H., Ahluwalia, Manmeet S., Ahmad, Shahjehan, Ahmed, A. Karim, Ahmed, Raheel, Aisiku, Imoigele P., Akbar, Muhammad A., Akram, Harith, Alaraj, Ali, Albrecht, Jennifer S., Albuquerque, Felipe C., Alexander, Michael J., Alexandrov, Andrei V., Alexopoulos, Andreas V., Ali, Zarina S., Al-Khalili, Kenan, Al-Mefty, Ossama, Al-Mefty, Rami O., Alnahhas, Iyad, Alrobaian, Malek, Al-Saiegh, Fadi, Alterman, Ron L., Altshuler, David B., Amenta, Peter S., Ames, Christopher P., Amin-Hanjani, Sepideh, Ammirati, Mario, Andaluz, Norberto, Anderson, Richard C.E., Andrade, Pablo, Ares, William J., Arle, Jeffrey E., Arnaout, Omar, Arnold, Paul M., Assina, Rachid, Aszmann, Oskar C., Attenello, Frank J., III, Attia, Albert, Avellino, Anthony M., Awad, Issam A., Ayantayo, Temitayo O., Bader, Edward R., Badhiwala, Jetan H., Baehring, Joachim M., Bagic´, Anto I., Bagley, Stephen J., Bai, Michael Y., Bailes, Julian E., Bain, Mark, Baker, Turner, Ball, Perry A., Ballester, Leomar Y., Balu, Ramani, Ban, Vin Shen, Barak, Tanyeri, Baranoski, Jacob F., Barbaro, Nicholas M., Barber, Sean M., Barker, Frederick G., II, Barnett, Gene H., Barone, Constance M., Barrow, Daniel Louis, Basma, Jaafar, Batchelor, Tracy T., Batjer, H. Hunt, Beattie, Michael S., Beaumont, Andrew, Beaumont, Thomas L., Bederson, Joshua B., Belani, Puneet, Belzberg, Allan J., Benet, Arnau, Ben-Haim, Sharona, Berenstein, Alejandro, Berga, Sarah L., Berger, Mitchel S., Bergsneider, Marvin, Bernstock, Joshua D., Bhatia, Sanjay, Bi, Wenya Linda, Bigder, Mark G., Bijlenga, Philippe, Bingaman, William, Birk, Harjus S., Bishop, Allen T., Blakeley, Jaishri O., Blomstedt, Patric, Blue, Rachel, Blumenthal, Scott, Boaro, Alessandro, Boddu, James V., Bohnen, Angela, Bok, Arnold P., Boone, Myles D., Boop, Frederick A., Boszczyk, Bronek M., Bowyer, Susan M., Brahimaj, Bledi C., Brem, Henry, Brem, Steven, Bresnahan, Jacqueline C., Brinjikji, Waleed, Brinkmann, Benjamin H., Brînzeu, Andrei, Britz, Gavin W., Brockmeyer, Douglas L., Brown, Desmond A., Brown, Justin M., Brown, Matthew T., Brown, Robert D., Jr., Bruce, Jeffrey N., Bruckman, Karl C., Bruhat, Alexis, Brunstrom-Hernandez, Janice E., Brunswick, Andrew, Bruzek, Amy K., Buchanan, Ian A., Budohoski, Karol P., Buell, Thomas J., Büki, András, Bunevicius, Adomas, Burchiel, Kim J., Bydon, Mohamad, Byrne, Richard W., Cabrejo, Raysa, Cabrilo, Ivan, Cahill, Daniel P., Caplan, Justin M., Carlson, Andrew P., Carrión-Penagos, Julián, Carroll, Benjamin W., Cascino, Gregory D., Castaneyra-Ruiz, Leandro, Castinetti, Frederic, Cavalcanti, Daniel D., Cawley, C. Michael, Cernak, Ibolja, Cetas, Justin S., Chan, Michael D., Ka-Ying Chan, Vivien, Chang, Chih-Chang, Chang, Louis, Chang, Steven D., Charbel, Fady T., Charest-Morin, Raphaële, Chari, Aswin, Chaudhary, Navjot, Chauvel, Patrick, Chen, Kevin S., Chen, Liang, Cheng, Joseph, Cherian, Jacob, Cheung, Kenneth M.C., Cheyuo, Cletus, Chiang, Veronica L., Chiarelli, Peter A., Chiocca, E. Antonio, Chitale, Rohan V., Cho, Catherine, Choi, Heejung, Chou, Dean, Christian, Cindy W., Christiansen, Peter A., Church, Ephraim W., Clarke, Jennifer L., Cleary, Daniel R., Clune, James E., Cohen, Justin D., Cohen-Inbar, Or, Colasanti, Roberto, Collins, John M., Comair, Youssef G., Conner, Andrew K.P., Connolly, E. Sander, Jr., Cooper, Jared B., Corcos, Daniel Montie, Coric, Domagoj, Costa, Anthony B., Couldwell, William T., Crino, Peter B., Crofton, Andrew R., Cullen, D. Kacy, Curt, Armin, Dacey, Ralph G., Jr., Daci, Rrita, Dailey, Andrew T., D’Alessandris, Quintino Giorgio, Damisah, Eyiyemisi C., Daniels, David J., Das, Sunit, Davanzo, Justin R., David, Carlos A., David, David J., Davidson, Benjamin, Davis, Gavin A., Day, Arthur L., Dea, Nicolas, De Donato, Giuseppe, Deiner, Stacie, De la Garza, Carlos, Delavari, Nader, Del Brutto, Oscar H., Delman, Bradley N., DeLong, Mahlon R., DeMonte, Franco, de Oliveira, Evandro, Derman, Peter B., Desai, Arati, Deshpande, Krutika, Diaz, Michele, Diaz-Arrastia, Ramon R., DiGiorgio, Anthony M., DiLuna, Michael L., DiMeco, Francesco, Dlouhy, Brian J., Doğruel, Yücel, Donahue, Joseph H., Donoho, Daniel A., Doshi, Amish H., Dreier, Jens P., Driver, Joseph, Drofa, Alexander, Ducruet, Andrew F., Duffau, Hugues, Duhaime, Ann-Christine, Dumont, Aaron S., Duncan, John S., Dunn, Gavin P., Dunn, Ian F., Eberwine, James H., Eckardt, Gerald W., Edem, Idara J., Edwards, Michael S.B., Egemen, Emrah, Eisenbarth, Rachel, Eisenberg, Howard, Elder, J. Bradley, Elhammady, Mohamed Samy, Elias, W. Jeffrey, Ellingson, Benjamin M., Ellis, Jason A., Elswick, Clay M., Emch, Todd M., Emerson, Samuel, Ene, Chibawanye I., Englot, Dario J., Erdman, John H., III, Eskandari, Ramin, Essayed, Walid Ibn, Everson, Richard G., Fadul, Camilo E., Fan, Yi, Farina, Dario, Farrell, Christopher J., Feghali, James, Fehlings, Michael G., Fehnel, Katie Pricola, Feigin, Valery L., Feldman, Eva L., Feldman, Michael J., Feldstein, Neil, Fenno, Lief E., Ferguson, Adam R., Feroze, Abdullah H., Fessler, Richard G., Filler, Aaron G., Findlay, J. Max, Finn, Michael A., Finnell, Richard H., Fisher, Charles G., Flamm, Eugene S., Flanders, Tracy M., Flemming, Kelly D., Flores-Sarnat, Laura, Follett, Kenneth A., Fontes, Ricardo B.V., Ford, Paul J., Foreman, Brandon P., Foreman, Paul M., Fornoff, Linden E., Fouda, Mohammed A., Foyouzi, Nastaran, Franco, Daniel, Franzini, Andrea, Fridley, Jared S., Friedlander, Robert M., Frisoli, Fabio A., Fry, Donald E., Gregory Fu, Kai-Ming, Fujita, Naohide, Fulbright, Robert K., Fulkerson, Daniel H., Fuller, Gregory N., Fusco, Matthew R., Galanopoulou, Aristea S., Gallagher, Gary W., Galvan, Adriana, Gander, Phillip E., Gandhi, Chirag D., Gao, Guoyi, Garcia, Hector H., García, Paul S., Gardner, Paul A., Gardner, Raquel C., Garzon-Muvdi, Tomas, Gavin, Cormac G., Gea-Banacloche, Juan C., George, Timothy M., Georgoulis, George D., Gerard, Carter S., Gerety, Patrick A., Gerszten, Kristina, Gerszten, Peter C., Ghaith, Abdul Karim, Ghatan, Saadi, Ghobrial, George M., Ghogawala, Zoher, Ghosh, Chaitali, Giacino, Joseph T., Giacobbe, Peter, Gianaris, Thomas J., Giannotta, Steven L., Giglio, Pierre, Gilad, Ronit, Gill, Brian J.A., Gillick, John L., Gilmer, Holly S., Gjedde, Albert H., Glenn, Chad A., Godil, Saniya S., Goel, Atul, Gokaslan, Ziya L., Goldberg, Jacob L., Goldstein, Hannah E., Golub, Danielle, Gonzalez, Glenn A., Gonzalez-Martinez, Jorge Á., Goodden, John R., Goodman, J. Clay, Goodrich, James Tait, Goodwin, C. Rory, Gordon, David S., Gottfried, Oren N., Goumnerova, Liliana C., Goyal, Anshit, Grady, M. Sean, Graffeo, Christopher S., Grafman, Jordan H., Gragnaniello, Cristian, Grande, Andrew W., Grant, Gerald A., Grebenciucova, Elena, Greenfield, Jeffrey, Grimaudo, Heather C., Groff, Michael W., Gross, Robert E., Grossman, Rachel, Groves, Mari L., Gstoettner, Clemens, Guenette, Jeffrey P., Günel, Murat, Gupta, Nalin, Gutman, Matthew J., Guyer, Richard D., Hachem, Laureen D., Haddad, Georges F., Hadjipanayis, Constantinos G., Hafez, Daniel M., Hagan, John P., Haglund, Michael M., Haines, Stephen J., Haldeman, Clayton L., Halvorson, Kyle G., Hamberger, Marla J., Hamdi, Hussein, Hamilton, D. Kojo, Hamilton, Kimberly M., Hamilton, Mark G., Hankinson, Todd C., Haq, Ihtsham ul, Harbaugh, Robert E., Hardesty, Douglas A., Hardigan, Trevor, Hariz, Marwan, Harrigan, Mark R., Harrop, James S., Hartings, Jed A., Härtl, Roger, Harward, Stephen C., II, Hasbun, Rodrigo, Hawryluk, Gregory W.J., Hayman, Erik, Hayward, Richard D., He, Lucy, Healy, Andrew T., Heary, Robert F., Heiden, Petra, Heinricher, Mary M., Heller, Robert S., Retel Helmrich, Isabel R.A., Helmy, Adel, Heman-Ackah, Sabrina M., Hendricks, Benjamin K., Herendeen, John S., Heros, Roberto C., Herrup, Karl, Hervey-Jumper, Shawn L., Heuer, Gregory G., Heyer, Eric J., Higuchi, Yoshinori, Hillary, Frank G., Ho, Winson S., Hoang, Nguyen, Hoang, Stanley, Hoelscher, Christian, Hoffer, S. Alan, Hofstetter, Christoph, Holland, Eric C., Holland, Ryan M., Holste, Katherine, Hongo, Kazuhiro, Horisawa, Shiro, Horner, Philip J., Howard, Matthew A., III, Hsueh, Brian, Huang, Judy, Huang, Kevin T., Huang, Michael C., Huang, Raymond Y., Hudgins, Eric, Huguenard, Anna, Hunt, Matthew A., Hurlbert, R. John, Hussein, Ahmed E., Hutchinson, Peter J., Huttner, Anita, Huys, Daniel, Hwang, Steven W., Iaccarino, Mary A., Ibrahim, Mohab, Iliff, Jeffrey J., Ilyas, Adeel, Ingram, Susan L., Isaacs, Albert M., Isaias, Ioannis U., Iskandar, Bermans J., Iyer, Aditya K., Jabbour, Pascal, Jackson, Christopher M., Jadhav, Ashutosh P., Jakobs, Martin, Jallo, George I., Jane, John A., Jr., Janigro, Damir, Jankowitz, Brian T., Jea, Andrew, Jehi, Lara, Jellinger, Kurt A., Jenson, Amanda V., Jho, Diana, Jiang, Bowen, Jiang, Fan, Jimenez, David F., Jimenez, Lincoln, Jin, Haiyan, Jo, Jasmin T., Johanson, Conrad E., Johnson, Luke A., Johnson, Mark D., Johnson, Nathaniel, Jones, Adrian C., Jones, Kristen E., Jones, Tuckerman, Joseph, Jacob R., Joshi, Krishna C., Joshi, Rushikesh S., Jovin, Tudor G., Julian, Alex, Juraschka, Kyle, Abdo do Seixo Kadri, Paulo, Kalani, M. Yashar S., Kalanithi, Paul S.A., Kalfas, Iain H., Kalnins, Aleksandrs Uldis, Kamath, Ashwin A., Kanev, Paul M., Kang, Daniel G., Kang, James D., Kanter, Adam S., Kaplitt, Michael G., Kappel, Ari D., Karikari, Isaac, Karsy, Michael, Kasliwal, Manish K., Kaufmann, Anthony M., Kawasaki, Hiroto, Kellner, Christopher P., Kelly, Alexander P., Kemeny, Andras A., Kestle, John R.W., Khalsa, Siri S., Khan, Imad S., Khan, Nadia, Khan, Tariq, Khanna, Omaditya, Khanna, Ryan, Kigerl, Kristina A., Kim, Dong H., Kim, Louis J., Kim, Paul K., Kim, Thomas A., Kim, Won, Kirnaz, Sertaç, Kirsch, Wolff, Kitchen, Neil D., Klein, Joshua P., Kliot, Michel, Knightly, John J., Knisely, Jonathan, Knopman, Jared, Ko, Andrew L., Kobayashi, Katsuya, Kobets, Andrew J., Koch, Matthew J., Kocharian, Gary, Koerner, John D., Kohara, Kotaro, Kohn, Max, Kolias, Angelos G., Koo, Clara S., Kosztowski, Thomas, Kotecha, Rupesh R., Kovach, Christopher K., Kraemer, Mark R., Krauss, Joachim K., Krieg, Sandro M., Krieger, Mark D., Krishnaney, Ajit A., Ksendzovsky, Alexander, Kulkarni, Abhaya V., Vijay Kumar, Gomatam R., Kumar, Sachin A., Kung, David K., Kuo, Jeffrey V., Kvint, Svetlana, Kwan, Kenny, Issa Laack, Nadia N., Ladner, Travis R., Lafage, Renaud, Lafage, Virginie, Lam, Arthur M., Lamm, Adam G., Landazuri, Patrick, Lanzino, Giuseppe, Larson, Paul, Lau, Catherine Y., Lau, Darryl, Lavine, Sean D., Lawler, Sean E., Laws, Edward R., Jr., Lawton, Michael T., Laxpati, Nealen G., Lebed, Brett D., Lee, Cheng-Chia, Lee, Jonathan J., Lee, Ryan P., Lee, Sangmi, Lehman, Ronald A., Jr., Lenke, Lawrence G., Le Roux, Peter D., Leuthardt, Eric C., Levin, Emily, Levy, Elad I., Lewis, Evan M., Lhatoo, Samden, Li, Dianyou, Li, Yingda, Ching Ng, Angela Li, Liau, Linda M., Liebenow, Brittany, Lieberman, Isador H., Limbrick, David D., Jr., Lin, Emily, Lin, Kant Y., Lin, Zhengyu, Lingsma, Hester F., Linskey, Mark E., Lipsman, Nir, Litvack, Zachary N., Liu, James K.C., Liu, Kenneth C., Liu, Wei, Lober, Robert M., Lohkamp, Laura-Nanna, Lonser, Russell R., Louvi, Angeliki, Lozano, Andres M., Lu, Victor M., Luciano, Mark G., Lukas, Rimas V., Luo, Lan, Ma, Lijun, Maas, Andrew I.R., Macdonald, R. Loch, Mack, William J., Mackey, Kimberly A., Macki, Mohamed, MacLachlan, Lara S., Madarash, Holly Oemke, Madsen, Peter J., Maegele, Marc, Magistretti, Pierre J., Mahan, Mark A., Maher, Cormac O., Mahtabfar, Aria, Majeed, Kashif, Makarenko, Serge, Makley, Amy T., Malessy, Martijn J.A., Malik, Athar N., Mallucci, Conor, Mambelli, Dorian D., Mammi, Marco, Mangano, Francesco T., Maniker, Allen H., Manley, Geoffrey T., Manolidis, Spiros, Maroon, Joseph C., Martin, Alastair, Martin, Neil A., Martirosian, Vahan, Martirosyan, Nikolay L., Maslink, Colin, Massie, Lara, Mathur, Amit M., Matias, Caio M., Mauer, Kimberly M., Maulucci, Christopher M., Maurer, Robert K., Mazur, Marcus D., Mazwi, Nicole, McAllister, James P., II, McClain, Craig D., McCormack, Ryan M., McCrea, Michael A., McCutcheon, Ian E., McDermott, Michael W., McDougall, Cameron G., McDougall, Cameron M., McEvoy, Andrew W., McGrath, Hari, McGrath, Lynn, Jr., McKhann, Guy M., McMahon, J. Tanner, McPheeters, Matthew J., Meaney, David F., Medel, Ricky, Medress, Zachary, Mehta, Minesh P., Menacho, Sarah T., Menezes, Arnold H., Menon, David K., Mergeche, Joanna L., Meyer, Fredric B., Meyer, Jenna, Meyer, Scott A., Meyers, Philip M., Midha, Rajiv, Miller, Charles A., Miller, Jonathan P., Miller, Neil R., Mirza, Farhan A., Mirzadeh, Zaman, Miserocchi, Anna, Misra, Basant K., Missios, Symeon, Miyagishima, Danielle F., Miyashiro, Kevin Y., Mizuno, Junichi, Mizuno, Shuichi, Mocco, J., Mohyeldin, Ahmed, Mokin, Maxim, Molinaro, Annette M., Moliterno, Jennifer, Monteith, Stephen J., Montenegro, Thiago S., Mooney, Michael A., Moosa, Shayan, Morales, Diego M., Morgan, Clinton D., Morgan, Isabella, Morgan, Michael Kerin, Mortimer, Vance R., Moss, Nelson, Moss, S. David, Mukherjee, Pratik, Mummaneni, Praveen V., Munich, Stephan A., Muraszko, Karin, Murthy, Saikiran G., Mushlin, Harry, Mussi, Antônio C.M., Nagel, Sean J., Nagy, Gábor, Nair, Dileep R., Najm, Imad M., Nakaji, Peter, Nakajima, Takeshi, Nasser, Rani, Nater, Anick, Navarro, Jovany Cruz, Nayak, Lakshmi, Neira, Justin A., Nelson, Lindsay D., Neman, Josh, Newell, David W., Nguyen, James H., Ngwenya, Laura Benjamin, Nicolato, Antonio, Nimjee, Shahid M., Nishimura, Sayoko, Niu, Tianyi, Norris, Scott A., Noureldine, Mohammad Hassan A., Nurmikko, Turo J., Nuwer, Marc R., Oberheim-Bush, Nancy Ann, Ochiai, Taku, Oh, Nathan, Oh, Taemin, Okonkwo, David O., Okun, Michael S., Oldfield, Edward H., Brigid O’Leary, Joanna Shawn, Olivi, Alessandro, O’Neill, Francis, Oppenlander, Mark E., Osbun, Joshua W., O’Toole, John E., Özduman, Koray, Ozpinar, Alp, Pain, Margaret, Palacios, Eva M., Palmer, James N., Pamir, M. Necmettin, Pamoukian, Vicken, Panesar, Sandip S., Panov, Fedor E., Paramasivam, Srinivasan, Park, Christine, Park, Jon, Park, Paul, Park, T.S., Parker, Whitney E., Parsa, Andrew T., Partington, Michael D., Patel, Aman B., Patel, Bhuvic, Patel, Smruti K., Patel, Vaibhav M., Patil, Parag G., Payne, Russell, Peeters, Sophie M., Pekmezci, Melike, Pendharkar, Arjun V., Penn, Richard Deren, Pennicooke, Brenton H., Pennington, Zach, Della Pepa, Giuseppe Maria, Perin, Alessandro, Perlmutter, Joel S., Persing, J. Scott, Persing, John A., Persing, Sarah M., Peters, Matthew E., Petersen, Erika A., Petrov, Dmitriy, Pham, Martin, Picht, Thomas, Piepmeier, Joseph M., Pikis, Stylianos, Pilcher, Webster H., Pinckard-Dover, Heather N., Pineda, José A., Pinter, Joseph D., Pisculli, Mary L., Pittman, Thomas, Plesnila, Nikolaus, Pollack, Ian F., Pollock, Bruce E., Polly, David W., Jr., Polster, Sean P., Popovich, Phillip G., Post, Kalmon D., Potts, Matthew B., Pouratian, Nader, Powers, Alexander K., Prager, Briana C., Prashant, Giyarpuram N., Prestigiacomo, Charles J., Prevedello, Daniel M., Proctor, Mark R., Prolo, Laura M., Prost, Robert W., Puduvalli, Vinay K., Purger, David A., Qualmann, Krista J., Quiñones-Hinojosa, Alfredo, Raffa, Scott J., Raghavan, Prashant, Rahal, Jason Pierce, Rajappa, Prajwal, Ram, Zvi, Ranjan, Manish, Rao, Ganesh, M.S. Raper, Daniel, Rapoport, Benjamin I., Raskin, Jeffrey S., Raslan, Ahmed M., Rasmussen, Peter, Rasouli, Jonathan J., Ravindra, Vijay M., Ray, Dibyendu K., Ray, Wilson Z., Raz, Eytan, Raza, Shaan M., Régis, Jean, Reilly, Peter L., Reith, Florence C.M., Rennert, Robert C., Resnick, Daniel K., Reynolds, Renée, Rezai, Ali R., Rhines, Laurence D., Rhoton, Albert L., Jr., Ribalta, Teresa, Richardson, R. Mark, Riggins, Gregory J., Riina, Howard A., Rinaldo, Lorenzo, Rincon-Torroella, Jordina, Ringer, Andrew J., Riva-Cambrin, Jay, Rizk, Elias, Robert, Stephanie M., Robertson, Claudia, Robertson, Jon H., Robinson, Leslie C., Robinson, Michael W., Robinson, Shenandoah, Roche, Aidan D., Roche, Pierre-Hugues, Rogg, Jeffrey M., Roguski, Marie, Roland, Jarod L., Rolston, John D., Rosenberg, William S., Rosenow, Joshua M., Rosenthal, Guy, Rosenwasser, Robert H., Roser, Florian, Rosner, Michael K., Rosseau, Gail, Rossi, Vincent J., Rovner, Eric S., Rubiano, Andres M., Rubio, Roberto Rodriguez, Rucker, Janet C., Rui, Yanning, Russin, Jonathan J., Rutka, James T., Saadeh, Yamaan S., Saatian, Behnaz, Sack, Kenneth D., Sader, Nicholas, Safaee, Michael M., Safain, Mina G., Sagher, Oren, Sahgal, Arjun, Saigal, Rajiv, Saito, Nobuhito, Saleh, Mohamed, Salinas, Ryan D., Salminger, Stefan, Samarage, H. Milan, Samdani, Amer F., Sand, Lauren A., Sani, Sepehr, Sankaran, Sujatha, Sansur, Charles A., Santarius, Thomas, Santiago, Paul, Santiago-Dieppa, David R., Santiago-Sim, Teresa, Sarkiss, Christopher A., Sarnat, Harvey B., Sarris, Christina E., Sather, Michael, Savastano, Luis E., Sawaya, Raymond, Schaller, Karl, Schiff, Nicholas D., Schipmann, Stephanie, Schlachter, Leslie, Schlesinger, David J., Schmidt, Franziska A., Schmidt, Meic H., Schneider, Lonnie, Schramm, Johannes, Schuele, Stephan U., Schulder, Michael, Schupper, Alexander J., Schwab, Frank J., Schwartz, Theodore H., Sciubba, Daniel M., Scott, R. Michael, Scullen, Tyler A., Selden, Nathan R., Sellin, Jonathan N., Selman, Warren R., Sen, Chandranath, Serizawa, Toru, Serrone, Joseph C., Sgubin, Donatella, Shaffrey, Christopher I., Shah, Kushal J., Shah, Lubdha M., Shah, Manish N., Shahlaie, Kiarash, Shapiro, Maksim, Sharan, Ashwini, Sharma, Deepak, Sharma, Mohan R., Sheehan, Jason P., Sheehan, Jonas M., Sheikhi, Lila, Shiflett, James M., Shigamatsu, Tomoyoshi, Shilpakar, Sushil Krishna, Shils, Jay L., Shimony, Nir, Shin, Alexander Y., Siddiqui, Adnan H., Sidhu, Meneka K., Silveira, Luke A., Silver, Jerry, Sindou, Marc, Singh, Jeffrey M., Singh, Manish K., Sizdahkhani, Saman, Skirboll, Stephen, Slavin, Justin, Smith, Brandon W., Smith, Edward R., Smith, Justin S., Smith, Kris A., Smith, Luke G.F., Smith, Timothy R., Smith, Yoland, Solomon, David A., Solomon, Robert A., Soltys, Scott G., Somji, Mohamed, Sorenson, Jeffrey M., Soriano, Sulpicio G., Sorscher, Michelle, Souweidane, Mark M., Spencer, Dennis D., Spetzler, Robert F., Spinazzi, Eleonora F., Spinner, Robert J., Sribnick, Eric A., Srinivasan, Visish M., Stabingas, Kristen, Stapleton, Christopher J., Starke, Robert M., Starr, Philip, St. Clair, Eric G., Stedelin, Brittany, Stefko, S. Tonya, Steinberg, Gary K., Stern, Matthew A., Steyerberg, Ewout W., Stieg, Philip E., Stone, Scellig S.D., Stoodley, Marcus, Strahle, Jennifer M., Stricsek, Geoffrey, Strong, Anthony, Strowd, Roy E., III, Stummer, Walter, Su, YouRong S., Sughrue, Michael E., Suh, John H., Sulaiman, Wale A.R., Sun, Bomin, Sun, Matthew Z., Sun, Xiaonan Richard, Sundaram, Vikram K., Sweid, Ahmad, Syed, Hasan R., Tagliati, Michele, Taira, Takaomi, Tajsic, Tamara, Takagi, Yasushi, Takeoka, Yoshiki, Tamargo, Rafael J., Tanaka, Shota, Tandon, Nitin, Tang, Daniel D., Tanweer, Omar, Tate, Matthew C., Tatsui, Claudio E., Taylor, Jennie W., Taylor, Jesse A., Taylor, Michael D., Templer, Jessica W., Teo, Charles, Tessier, Jeffrey M., Theadom, Alice, Theodore, Nicholas, Thinwa, Josephine W., Thompson, B. Gregory, Jr., Thompson, Eric M., Thompson, Stephen A., Thon, Niklas, Thurtell, Matthew J., Tilton, Ann H., Timmons, Shelly D., Tonn, Jörg-Christian, Toth, Gabor, Toussaint, Charles P., Tran, Minh H., Trapp, Bruce D., Traylor, Jeffrey I., Trifiletti, Daniel M., Tse, Kai-Hei, Tubbs, R. Shane, Tuleasca, Constantin, Tunkel, Allan R., Türe, Ugur, Umansky, Daniel, Unda, Santiago R., Ung, Timothy H., Upadhyayula, Pavan S., Uribe, Juan S., Uy, Benjamin R., Vaccaro, Alexander R., Vakharia, Kunal, Vakharia, Vejay N., Valvassori, Luca, van den Bent, Martin J., Van Gompel, Jamie J., Vasquez, Carlos M., Vasudeva, Viren S., Vasudevan, Kumar, Vellimana, Ananth K., Verlicchi, Angela, Vervoordt, Samantha M., Viapiano, Mariano S., Vide, Sérgio, Villa, Genaro R., Virk, Michael S., Visser-Vandewalle, Veerle, Vitek, Jerrold L., Vivas-Buitrago, Tito, Vo, Chau D., Vogelbaum, Michael A., Vollmer, Dennis G., Wackym, P. Ashley, Wainwright, Mark S., Wali, Arvin R., Walker, Corey T., Walters, Beverly C., Wang, Anthony C., Wang, Arthur, Wang, Huan, Wang, Joshua L., Wang, Kevin K.W., Wang, Michael Y., Wang, Minghao, Wang, Shelly, Wang, Tao, Wang, Tony R., Wang, Vincent Y., Waqas, Muhammad, Warf, Benjamin C., Weiner, Howard L., Weingart, Jon D., Weinstein, Lawrence, Weiss, Martin H., Weiss, Nirit, Welch, Babu G., Wellons, John C., III, Wen, Hung Tzu, Wen, Patrick Y., West, G. Alexander, Wewel, Joshua T., Whitehead, William E., Whiting, Alexander C., Whiting, Donald M., Wichmann, Thomas, Wilkinson, D. Andrew, Williams, Michael A., Williams-Medina, Alberto R., Williamson, Theresa, Wilson, Lindsay, Winer, Jesse L., Winfree, Christopher J., Winkler, Ethan A., Winn, H. Richard, Wintermark, Max, Wipplinger, Christoph, Witiw, Christopher D., Wolfla, Christopher E., Wolinsky, Jean-Paul, Wong, Eric T., Worrell, Gregory A., Wrensch, Margaret R., Wright, Christina H., Wu, Jau-Ching, Wu, Jenny, Wu, Kyle C., Wu, Pang Hung, Xu, David S., Xu, Linda Wei, Xu, Yifan, Xu, Zhen, Xu, Zhiyuan, Yaeger, Kurt A., Yahanda, Alexander T., Yan, Rachel E., Yan, Yuanqing, Yang, George L., Yasuno, Katsuhito, Yen, Chun-Po, Yokota, Kazuya, Yolcu, Yagiz Ugur, Young, Timothy P., Yu, Jennifer S., Yue, John K., Yuh, Esther L., Zabramski, Joseph M., Zacest, Andrew, Zacko, J. Christopher, Zada, Gabriel, Zafonte, Ross D., Zager, Eric L., Zakare-Fagbamila, Rasheedat T., Zakeri, Amanda, Zanotti, Bruno, Zawar, Ifrah, Zeineddine, Hussein A., Zellner, Elizabeth G., Zhan, Shikun, Zhang, Chencheng, Zhang, Michael, Zhang, Yingying, Zibly, Zion, Zigler, Jack E., Zipfel, Gregory J., Zipser, Carl Moritz, Zrinzo, Ludvic, and Zumofen, Daniel W.

Published
2023
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28. Loss of protocadherin-12 leads to Diencephalic-Mesencephalic Junction Dysplasia syndrome

Author

McEvoy-Venneri, Jennifer, Einhorn, Yaron, Guemez-Gamboa, Alicia, Heimer, Gali, Bilguvar, Kaya, Musaev, Damir, Shomron, Noam, Porat, Yuval, Akizu, Naiara, Gabriel, Stacey, Pillar, Nir, Issa, Mahmoud Y., Erson-Omay, Emine Z., Gregor, Anne, PER, HÜSEYİN, Ben-Zeev, Bruria, Gunel, Murat, Yasuno, Katsuhito, Fang, Rebecca, Copeland, Brett, Saleem, Sahar N., Rosti, Rasim Ozgur, Silhavy, Jennifer L., Belandres, Denice, Lewis, Steven M., Weissglas-Volkov, Daphna, Caglayan, Ahmet Okay, Akgumus, Gozde Tugce, Gumus, Hakan, Gleeson, Joseph G., Kumandas, Sefer, Stanley, Valentina, Bayram, Ayse Kacar, Schroth, Jana, and Zaki, Maha S.

Subjects
Male, Child, Preschool, Mutation, Infant, Newborn, Humans, Infant, Female, Cadherins, Child, Nervous System Malformations, Article, Protocadherins, Brain Stem
Abstract

Objective Methods To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome. Eight families with DMJD were studied by whole-exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression. Results Interpretation All patients showed biallelic mutations in the nonclustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth. DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions. Ann Neurol 2018;84:646-655

Published
2018

30. Loss of Protocadherin‐12 L eads to D iencephalic‐ M esencephalic J unction D ysplasia S yndrome

Author

Guemez‐Gamboa, Alicia, primary, Çağlayan, Ahmet Okay, additional, Stanley, Valentina, additional, Gregor, Anne, additional, Zaki, Maha S., additional, Saleem, Sahar N., additional, Musaev, Damir, additional, McEvoy‐Venneri, Jennifer, additional, Belandres, Denice, additional, Akizu, Naiara, additional, Silhavy, Jennifer L., additional, Schroth, Jana, additional, Rosti, Rasim Ozgur, additional, Copeland, Brett, additional, Lewis, Steven M., additional, Fang, Rebecca, additional, Issa, Mahmoud Y., additional, Per, Huseyin, additional, Gumus, Hakan, additional, Bayram, Ayse Kacar, additional, Kumandas, Sefer, additional, Akgumus, Gozde Tugce, additional, Erson‐Omay, Emine Z., additional, Yasuno, Katsuhito, additional, Bilguvar, Kaya, additional, Heimer, Gali, additional, Pillar, Nir, additional, Shomron, Noam, additional, Weissglas‐Volkov, Daphna, additional, Porat, Yuval, additional, Einhorn, Yaron, additional, Gabriel, Stacey, additional, Ben‐Zeev, Bruria, additional, Gunel, Murat, additional, and Gleeson, Joseph G., additional

Published
2018
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31. Genotype-phenotype investigation of 35 patients from 11 unrelated families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome

Author

Yilmaz, Saliha, primary, Uludağ Alkaya, Dilek, additional, Kasapçopur, Özgür, additional, Barut, Kenan, additional, Akdemir, Ekin S., additional, Celen, Cemre, additional, Youngblood, Mark W., additional, Yasuno, Katsuhito, additional, Bilguvar, Kaya, additional, Günel, Murat, additional, and Tüysüz, Beyhan, additional

Published
2018
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32. Additional file 1: of Longitudinal analysis of treatment-induced genomic alterations in gliomas

Author

E. Erson-Omay, Henegariu, Octavian, S. Omay, Akdes Harmancı, Youngblood, Mark, Ketu Mishra-Gorur, Li, Jie, Özduman, Koray, Geneive Carrión-Grant, Clark, Victoria, Çağlar, Caner, Bakırcıoğlu, Mehmet, M. Pamir, Tabar, Viviane, Vortmeyer, Alexander, Bilguvar, Kaya, Yasuno, Katsuhito, DeAngelis, Lisa, Baehring, Joachim M., Moliterno, Jennifer, and Günel, Murat

Abstract

Supplementary methods. (PDF 90 kb)

Published
2017
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33. Additional file 2: of Longitudinal analysis of treatment-induced genomic alterations in gliomas

Author

E. Erson-Omay, Henegariu, Octavian, S. Omay, Akdes Harmancı, Youngblood, Mark, Ketu Mishra-Gorur, Li, Jie, Özduman, Koray, Geneive Carrión-Grant, Clark, Victoria, Çağlar, Caner, Bakırcıoğlu, Mehmet, M. Pamir, Tabar, Viviane, Vortmeyer, Alexander, Bilguvar, Kaya, Yasuno, Katsuhito, DeAngelis, Lisa, Baehring, Joachim M., Moliterno, Jennifer, and Günel, Murat

Abstract

Supplementary figures. Figure S1 Circos plots of cases in the Yale-Glioma cohort that are identified to have gone through chromothripsis. Figure S2 ATG5 gene amplification through chromothripsis. Figure S3 Increased levels of MT group genes by a focal amplification in a whole-genome genotyping experiment. (PDF 465 kb)

Published
2017
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34. METAP1mutation is a novel candidate for autosomal recessive intellectual disability

Author

Caglayan, Ahmet Okay, Aktar, Fesih, Bilguvar, Kaya, Baranoski, Jacob F., Akgumus, Gozde Tugce, Harmanci, Akdes Serin, Erson-Omay, Emine Zeynep, Yasuno, Katsuhito, Caksen, Huseyin, and Gunel, Murat

Abstract

Intellectual disability (ID) is a genetic and clinically heterogeneous common disease and underlying molecular pathogenesis can frequently not be identified by whole-exome/genome testing. Here, we report four siblings born to a consanguineous union who presented with intellectual disability and discuss the METAP1pathway as a novel etiology of ID. Genomic analyses demonstrated that patients harbor a novel homozygous nonsense mutation in the gene METAP1. METAP1codes for methionine aminopeptidase 1 (MetAP1) which oversees the co-translational excision of the first methionine remnants in eukaryotes. The loss-of-function mutations to this gene may result in a defect in the translation of many essential proteins within a cell. Improper neuronal function resulting from this loss of essential proteins could lead to neurologic impairment and ID.

Published
2021
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37. ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features

Author

Çağlayan, Ahmet Okay, primary, Sezer, Rabia Gonul, additional, Kaymakçalan, Hande, additional, Ulgen, Ege, additional, Yavuz, Taner, additional, Baranoski, Jacob F., additional, Bozaykut, Abdulkadir, additional, Harmanci, Akdes Serin, additional, Yalcin, Yalim, additional, Youngblood, Mark W., additional, Yasuno, Katsuhito, additional, Bilgüvar, Kaya, additional, and Gunel, Murat, additional

Published
2017
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38. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

Author

Harmancı, Akdes Serin, primary, Youngblood, Mark W., additional, Clark, Victoria E., additional, Coşkun, Süleyman, additional, Henegariu, Octavian, additional, Duran, Daniel, additional, Erson-Omay, E. Zeynep, additional, Kaulen, Leon D., additional, Lee, Tong Ihn, additional, Abraham, Brian J., additional, Simon, Matthias, additional, Krischek, Boris, additional, Timmer, Marco, additional, Goldbrunner, Roland, additional, Omay, S. Bülent, additional, Baranoski, Jacob, additional, Baran, Burçin, additional, Carrión-Grant, Geneive, additional, Bai, Hanwen, additional, Mishra-Gorur, Ketu, additional, Schramm, Johannes, additional, Moliterno, Jennifer, additional, Vortmeyer, Alexander O., additional, Bilgüvar, Kaya, additional, Yasuno, Katsuhito, additional, Young, Richard A., additional, and Günel, Murat, additional

Published
2017
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39. Longitudinal analysis of treatment-induced genomic alterations in gliomas

Author

Erson-Omay, E. Zeynep, primary, Henegariu, Octavian, additional, Omay, S. Bülent, additional, Harmancı, Akdes Serin, additional, Youngblood, Mark W., additional, Mishra-Gorur, Ketu, additional, Li, Jie, additional, Özduman, Koray, additional, Carrión-Grant, Geneive, additional, Clark, Victoria E., additional, Çağlar, Caner, additional, Bakırcıoğlu, Mehmet, additional, Pamir, M. Necmettin, additional, Tabar, Viviane, additional, Vortmeyer, Alexander O., additional, Bilguvar, Kaya, additional, Yasuno, Katsuhito, additional, DeAngelis, Lisa M., additional, Baehring, Joachim M., additional, Moliterno, Jennifer, additional, and Günel, Murat, additional

Published
2017
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40. PPIL4is essential for brain angiogenesis and implicated in intracranial aneurysms in humans

Author

Barak, Tanyeri, Ristori, Emma, Ercan-Sencicek, A. Gulhan, Miyagishima, Danielle F., Nelson-Williams, Carol, Dong, Weilai, Jin, Sheng Chih, Prendergast, Andrew, Armero, William, Henegariu, Octavian, Erson-Omay, E. Zeynep, Harmancı, Akdes Serin, Guy, Mikhael, Gültekin, Batur, Kilic, Deniz, Rai, Devendra K., Goc, Nükte, Aguilera, Stephanie Marie, Gülez, Burcu, Altinok, Selin, Ozcan, Kent, Yarman, Yanki, Coskun, Süleyman, Sempou, Emily, Deniz, Engin, Hintzen, Jared, Cox, Andrew, Fomchenko, Elena, Jung, Su Woong, Ozturk, Ali Kemal, Louvi, Angeliki, Bilgüvar, Kaya, Connolly, E. Sander, Khokha, Mustafa K., Kahle, Kristopher T., Yasuno, Katsuhito, Lifton, Richard P., Mishra-Gorur, Ketu, Nicoli, Stefania, and Günel, Murat

Abstract

Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-transisomerase-like 4, in both familial and index IA cases. Ppil4depletion in vertebrate models causes intracerebral hemorrhage, defects in cerebrovascular morphology and impaired Wnt signaling. Wild-type, but not IA-mutant, PPIL4 potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator. These findings identify a novel PPIL4-dependent Wnt signaling mechanism involved in brain-specific angiogenesis and maintenance of cerebrovascular integrity and implicate PPIL4gene mutations in the pathogenesis of IA.

Published
2021
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41. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

Author

Harmanci, Akdes Serin, Youngblood, Mark W., Clark, Victoria E., Coskun, Sueleyman, Henegariu, Octavian, Duran, Daniel, Erson-Omay, E. Zeynep, Kaulen, Leon D., Lee, Tong Ihn, Abraham, Brian J., Simon, Matthias, Krischek, Boris, Timmer, Marco, Goldbrunner, Roland, Omay, S. Buelent, Baranoski, Jacob, Baran, Burcin, Carrion-Grant, Geneive, Bai, Hanwen, Mishra-Gorur, Ketu, Schramm, Johannes, Moliterno, Jennifer, Vortmeyer, Alexander O., Bilguevar, Kaya, Yasuno, Katsuhito, Young, Richard A., Guenel, Murat, Harmanci, Akdes Serin, Youngblood, Mark W., Clark, Victoria E., Coskun, Sueleyman, Henegariu, Octavian, Duran, Daniel, Erson-Omay, E. Zeynep, Kaulen, Leon D., Lee, Tong Ihn, Abraham, Brian J., Simon, Matthias, Krischek, Boris, Timmer, Marco, Goldbrunner, Roland, Omay, S. Buelent, Baranoski, Jacob, Baran, Burcin, Carrion-Grant, Geneive, Bai, Hanwen, Mishra-Gorur, Ketu, Schramm, Johannes, Moliterno, Jennifer, Vortmeyer, Alexander O., Bilguevar, Kaya, Yasuno, Katsuhito, Young, Richard A., and Guenel, Murat

Abstract

Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets.

Published
2017

42. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

Author

Massachusetts Institute of Technology. Department of Biology, Young, Richard A, Clark, Victoria E, Harmancı, Akdes Serin, Bai, Hanwen, Youngblood, Mark W, Lee, Tong Ihn, Baranoski, Jacob F, Ercan-Sencicek, A Gulhan, Abraham, Brian J, Weintraub, Abraham S, Hnisz, Denes, Simon, Matthias, Krischek, Boris, Erson-Omay, E Zeynep, Henegariu, Octavian, Carrión-Grant, Geneive, Mishra-Gorur, Ketu, Durán, Daniel, Goldmann, Johanna E, Schramm, Johannes, Goldbrunner, Roland, Piepmeier, Joseph M, Vortmeyer, Alexander O, Günel, Jennifer Moliterno, Bilgüvar, Kaya, Yasuno, Katsuhito, Günel, Murat, Young, Richard A., Massachusetts Institute of Technology. Department of Biology, Young, Richard A, Clark, Victoria E, Harmancı, Akdes Serin, Bai, Hanwen, Youngblood, Mark W, Lee, Tong Ihn, Baranoski, Jacob F, Ercan-Sencicek, A Gulhan, Abraham, Brian J, Weintraub, Abraham S, Hnisz, Denes, Simon, Matthias, Krischek, Boris, Erson-Omay, E Zeynep, Henegariu, Octavian, Carrión-Grant, Geneive, Mishra-Gorur, Ketu, Durán, Daniel, Goldmann, Johanna E, Schramm, Johannes, Goldbrunner, Roland, Piepmeier, Joseph M, Vortmeyer, Alexander O, Günel, Jennifer Moliterno, Bilgüvar, Kaya, Yasuno, Katsuhito, Günel, Murat, and Young, Richard A.

Abstract

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.

Published
2017

44. Integrated genomic characterization of IDH1-mutant glioma malignant progression

Author

Bai, Hanwen, Harmanci, Akdes Serin, Erson-Omay, E. Zeynep, Li, Jie, Coskun, Sueleyman, Simon, Matthias, Krischek, Boris, Ozduman, Koray, Omay, S. Buelent, Sorensen, Eric A., Turcan, Sevin, Bakirciglu, Mehmet, Carrion-Grant, Geneive, Murray, Phillip B., Clark, Victoria E., Ercan-Sencicek, A. Gulhan, Knight, James, Sencar, Leman, Altinok, Selin, Kaulen, Leon D., Guelez, Burcu, Timmer, Marco, Schramm, Johannes, Mishra-Gorur, Ketu, Henegariu, Octavian, Moliterno, Jennifer, Louvi, Angeliki, Chan, Timothy A., Tannheimer, Stacey L., Pamir, M. Necmettin, Vortmeyer, Alexander O., Bilguvar, Kaya, Yasuno, Katsuhito, Guenel, Murat, Bai, Hanwen, Harmanci, Akdes Serin, Erson-Omay, E. Zeynep, Li, Jie, Coskun, Sueleyman, Simon, Matthias, Krischek, Boris, Ozduman, Koray, Omay, S. Buelent, Sorensen, Eric A., Turcan, Sevin, Bakirciglu, Mehmet, Carrion-Grant, Geneive, Murray, Phillip B., Clark, Victoria E., Ercan-Sencicek, A. Gulhan, Knight, James, Sencar, Leman, Altinok, Selin, Kaulen, Leon D., Guelez, Burcu, Timmer, Marco, Schramm, Johannes, Mishra-Gorur, Ketu, Henegariu, Octavian, Moliterno, Jennifer, Louvi, Angeliki, Chan, Timothy A., Tannheimer, Stacey L., Pamir, M. Necmettin, Vortmeyer, Alexander O., Bilguvar, Kaya, Yasuno, Katsuhito, and Guenel, Murat

Abstract

Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors(1). To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways and upregulation of the FOXM1- and E2F2-mediated cell cycle transitions, as well as epigenetic silencing of developmental transcription factor genes bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extraterminal (BET) family as a potential therapeutic approach.

Published
2016

45. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

Author

Clarke, Victoria E., Harmanci, Akdes Serin, Bai, Hanwen, Youngblood, Mark W., Lee, Tong Ihn, Baranoski, Jacob F., Ercan-Sencicek, A. Gulhan, Abraham, Brian J., Weintraub, Abraham S., Hnisz, Denes, Simon, Matthias, Krischek, Boris, Erson-Omay, E. Zeynep, Henegariu, Octavian, Carrion-Grant, Geneive, Mishra-Gorur, Ketu, Duran, Daniel, Goldmann, Johanna E., Schramm, Johannes, Goldbrunner, Roland, Piepmeier, Joseph M., Vortmeyer, Alexander O., Gunel, Jennifer Molitemo, Bilguvar, Kaya, Yasuno, Katsuhito, Young, Richard A., Gunel, Murat, Clarke, Victoria E., Harmanci, Akdes Serin, Bai, Hanwen, Youngblood, Mark W., Lee, Tong Ihn, Baranoski, Jacob F., Ercan-Sencicek, A. Gulhan, Abraham, Brian J., Weintraub, Abraham S., Hnisz, Denes, Simon, Matthias, Krischek, Boris, Erson-Omay, E. Zeynep, Henegariu, Octavian, Carrion-Grant, Geneive, Mishra-Gorur, Ketu, Duran, Daniel, Goldmann, Johanna E., Schramm, Johannes, Goldbrunner, Roland, Piepmeier, Joseph M., Vortmeyer, Alexander O., Gunel, Jennifer Molitemo, Bilguvar, Kaya, Yasuno, Katsuhito, Young, Richard A., and Gunel, Murat

Abstract

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes(2,3), including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1,TRAF7, KLF4, AKT1, PIK3CA, and SMO4-8, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.

Published
2016

46. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

Author

Clark, Victoria E, primary, Harmancı, Akdes Serin, additional, Bai, Hanwen, additional, Youngblood, Mark W, additional, Lee, Tong Ihn, additional, Baranoski, Jacob F, additional, Ercan-Sencicek, A Gulhan, additional, Abraham, Brian J, additional, Weintraub, Abraham S, additional, Hnisz, Denes, additional, Simon, Matthias, additional, Krischek, Boris, additional, Erson-Omay, E Zeynep, additional, Henegariu, Octavian, additional, Carrión-Grant, Geneive, additional, Mishra-Gorur, Ketu, additional, Durán, Daniel, additional, Goldmann, Johanna E, additional, Schramm, Johannes, additional, Goldbrunner, Roland, additional, Piepmeier, Joseph M, additional, Vortmeyer, Alexander O, additional, Günel, Jennifer Moliterno, additional, Bilgüvar, Kaya, additional, Yasuno, Katsuhito, additional, Young, Richard A, additional, and Günel, Murat, additional

Published
2016
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47. Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

Author

Christofer Juhlin, C., Stenman, Adam, Haglund, Felix, Clark, Victoria E., Brown, Taylor C., Baranoski, Jacob, Bilguvar, Kaya, Goh, Gerald, Welander, Jenny, Svahn, Fredrika, Rubinstein, Jill C., Caramuta, Stefano, Yasuno, Katsuhito, Guenel, Murat, Backdahl, Martin, Gimm, Oliver, Söderkvist, Peter, Prasad, Manju L., Korah, Reju, Lifton, Richard P., Carling, Tobias, Christofer Juhlin, C., Stenman, Adam, Haglund, Felix, Clark, Victoria E., Brown, Taylor C., Baranoski, Jacob, Bilguvar, Kaya, Goh, Gerald, Welander, Jenny, Svahn, Fredrika, Rubinstein, Jill C., Caramuta, Stefano, Yasuno, Katsuhito, Guenel, Murat, Backdahl, Martin, Gimm, Oliver, Söderkvist, Peter, Prasad, Manju L., Korah, Reju, Lifton, Richard P., and Carling, Tobias

Abstract

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc., Funding Agencies|Stockholm County Council; StratCan, Karolinska Institutet, Stockholm; Agency for Science, Technology and Research, Singapore; Cancer Society in Stockholm, Sweden; Damon Runyon Cancer Research Foundation; Ohse Research Award

Published
2015
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48. Integrated genomic characterization of IDH1-mutant glioma malignant progression

Author

Bai, Hanwen, primary, Harmancı, Akdes Serin, additional, Erson-Omay, E Zeynep, additional, Li, Jie, additional, Coşkun, Süleyman, additional, Simon, Matthias, additional, Krischek, Boris, additional, Özduman, Koray, additional, Omay, S Bülent, additional, Sorensen, Eric A, additional, Turcan, Şevin, additional, Bakırcığlu, Mehmet, additional, Carrión-Grant, Geneive, additional, Murray, Phillip B, additional, Clark, Victoria E, additional, Ercan-Sencicek, A Gulhan, additional, Knight, James, additional, Sencar, Leman, additional, Altınok, Selin, additional, Kaulen, Leon D, additional, Gülez, Burcu, additional, Timmer, Marco, additional, Schramm, Johannes, additional, Mishra-Gorur, Ketu, additional, Henegariu, Octavian, additional, Moliterno, Jennifer, additional, Louvi, Angeliki, additional, Chan, Timothy A, additional, Tannheimer, Stacey L, additional, Pamir, M Necmettin, additional, Vortmeyer, Alexander O, additional, Bilguvar, Kaya, additional, Yasuno, Katsuhito, additional, and Günel, Murat, additional

Published
2015
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49. GENO-15IDENTIFICATION AND GENOMIC ANALYSIS OF HYPER-MUTATED AND ULTRA-MUTATED GBMS

Author

Erson-Omay, E. Zeynep, primary, Schultz, Nikolaus, additional, Omay, S. Bulent, additional, Ozduman, Koray, additional, Harmanci, Akdes Serin, additional, Clark, Victoria, additional, Baranoski, Jacob, additional, Gunel, Jennifer Moliterno, additional, Pamir, M. Necmettin, additional, Bilguvar, Kaya, additional, Yasuno, Katsuhito, additional, Vortmeyer, Alexander, additional, Huttner, Anita J., additional, Sander, Chris, additional, and Gunel, Murat, additional

Published
2015
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50. Whole‐exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

Author

Juhlin, C. Christofer, primary, Stenman, Adam, additional, Haglund, Felix, additional, Clark, Victoria E., additional, Brown, Taylor C., additional, Baranoski, Jacob, additional, Bilguvar, Kaya, additional, Goh, Gerald, additional, Welander, Jenny, additional, Svahn, Fredrika, additional, Rubinstein, Jill C., additional, Caramuta, Stefano, additional, Yasuno, Katsuhito, additional, Günel, Murat, additional, Bäckdahl, Martin, additional, Gimm, Oliver, additional, Söderkvist, Peter, additional, Prasad, Manju L., additional, Korah, Reju, additional, Lifton, Richard P., additional, and Carling, Tobias, additional

Published
2015
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