Your browser doesn't support javascript.
loading
De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei; King, Robert A; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J; Mandell, Jeffrey D; Huang, Alden Y; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E; Neale, Benjamin M; Coppola, Giovanni; Mathews, Carol A; Tischfield, Jay A; Scharf, Jeremiah M; State, Matthew W; Heiman, Gary A.
  • Willsey AJ; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA.
  • Fernandez TV; Yale Child Study Center and Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Yu D; Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • King RA; Yale Child Study Center and Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Dietrich A; University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, 9713GZ Groningen, the Netherlands.
  • Xing J; Rutgers, the State University of New Jersey, Department of Genetics and the Human Genetics Institute of New Jersey, Piscataway, NJ 08854, USA.
  • Sanders SJ; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA.
  • Mandell JD; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA.
  • Huang AY; Department of Neurology, University of California Los Angeles, Los Angeles, California, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Richer P; Yale Child Study Center and Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Sewanee: The University of the South, Sewanee, TN 37383, USA.
  • Smith L; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA.
  • Dong S; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA.
  • Samocha KE; Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Neale BM; Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Coppola G; Department of Neurology, University of California Los Angeles, Los Angeles, California, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Mathews CA; Department of Psychiatry, University of Florida School of Medicine, Gainesville, FL 32611, USA.
  • Tischfield JA; Rutgers, the State University of New Jersey, Department of Genetics and the Human Genetics Institute of New Jersey, Piscataway, NJ 08854, USA.
  • Scharf JM; Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic a
  • State MW; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.state@ucsf.edu.
  • Heiman GA; Rutgers, the State University of New Jersey, Department of Genetics and the Human Genetics Institute of New Jersey, Piscataway, NJ 08854, USA. Electronic address: heiman@dls.rutgers.edu.
Neuron ; 94(3): 486-499.e9, 2017 May 03.
Article en En | MEDLINE | ID: mdl-28472652
ABSTRACT
Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. VIDEO ABSTRACT.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteínas / Síndrome de Tourette / Cadherinas / Fibronectinas / Receptores de Superficie Celular / Péptidos y Proteínas de Señalización Intracelular Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Child / Female / Humans / Male Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteínas / Síndrome de Tourette / Cadherinas / Fibronectinas / Receptores de Superficie Celular / Péptidos y Proteínas de Señalización Intracelular Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Child / Female / Humans / Male Idioma: En Año: 2017 Tipo del documento: Article