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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | O'Rawe, Jason A. Ospina, Sandra Swensen, Jeffrey Monaghan, Kristin G. Smith, Rosemarie Martinez, Francisco Lyon, Gholson J. Katsanis, Nicholas Jiménez-Barrón, Laura T. Den Hollander, Nicolette Caro-Llopis, Alfonso Kousi, Maria Hufnagel, Robert B. Parboosingh, Jillian S. Ellingwood, Sara Dörfel, Max J. Crain, Jonathan Kosma, Konstantina Highnam, Gareth Innes, A. Micheil Kitsiou-Tzeli, Sophia Rosello, Monica Fang, Han Orellana, Carmen Metcalfe, Kay Kleefstra, Tjitske Roubertie, Agathe Yang, Edward Kalscheuer, Vera M. Moon, Sungjin Stegmann, Sander Robison, Reid Davis, Erica E. Au, P. Y. Billie Rivière, Jean-Baptiste Keegan, Catherine E. Prada, Carlos E. Rope, Alan F. Faivre, Laurence Wu, Yiyang Mittelman, David Wang, Edith H. Monfort, Sandra Oltra, Silvestre Tzetis, Maria Schuette, Jane L. Wang, Kai Smith, Christopher S. |
| Description | Country affiliation: United States Author Affiliation: O'Rawe JA ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA); Wu Y ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA); Dörfel MJ ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.); Rope AF ( Department of Medical Genetics, Northwest Kaiser Permanente, Portland, OR 97227, USA.); Au PY ( Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T3B 6A8, Canada.); Parboosingh JS ( Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T3B 6A8, Canada.); Moon S ( Center for Human Disease Modeling, Duke University, Durham, NC 27708, USA.); Kousi M ( Center for Human Disease Modeling, Duke University, Durham, NC 27708, USA.); Kosma K ( Department of Medical Genetics, Medical School, University of Athens, Athens 11527, Greece); Smith CS ( Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T3B 6A8, Canada.); Tzetis M ( Department of Medical Genetics, Medical School, University of Athens, Athens 11527, Greece); Schuette JL ( Department of Pediatrics, Division of Genetics, University of Michigan, Ann Arbor, MI 48109, USA); Hufnagel RB ( Division of Human Genetics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA); Prada CE ( Division of Human Genetics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA); Martinez F ( Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain.); Orellana C ( Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain.); Crain J ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.); Caro-Llopis A ( Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain.); Oltra S ( Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain.); Monfort S ( Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain.); Jiménez-Barrón LT ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA); Swensen J ( Caris Life Sciences, Phoenix, AZ 85040, USA.); Ellingwood S ( Division of Genetics, Pediatric Specialty Care, Maine Medical Partners, ME 04102, USA.); Smith R ( Department of Pediatrics, Division of Genetics, Barbara Bush Children's Hospital, Maine Medical Center, Portland, ME 04102, USA.); Fang H ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.); Ospina S ( Fundacion Cardioinfantil and Universidad del Rosario, Bogota 681004, Colombia.); Stegmann S ( Deptartment of Clinical Genetics, 6202 AZ Maastricht, the Netherlands.); Den Hollander N ( Department of Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.); Mittelman D ( Gene by Gene Ltd., Houston, TX 77008, USA.); Highnam G ( Gene by Gene Ltd., Houston, TX 77008, USA.); Robison R ( Utah Foundation for Biomedical Research, Salt Lake City, UT 84107, USA); Yang E ( Department of Radiology, Boston Children's Hospital, Boston, MA 02115, USA.); Faivre L ( Génétique des Anomalies du Développement EA4271, Université Bourgogne Franche-Comté, 21000 Dijon, France); Roubertie A ( Institut des Neurosciences de Montpellier, Université de Montpellier, BP 74103, 34950 Montpellier Cedex 5, France); Rivière JB ( Génétique des Anomalies du Développement EA4271, Université Bourgogne Franche-Comté, 21000 Dijon, France.); Monaghan KG ( GeneDx, Gaithersburg, MD 20877, USA.); Wang K ( Zilkha Neurogenetic Institute, Department of Psychiatry and Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.); Davis EE ( Center for Human Disease Modeling, Duke University, Durham, NC 27708, USA.); Katsanis N ( Center for Human Disease Modeling, Duke University, Durham, NC 27708, USA.); Kalscheuer VM ( Research Group Development and Disease, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.); Wang EH ( Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.); Metcalfe K ( Clinical Genetics Service, Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.); Kleefstra T ( Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.); Innes AM ( Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T3B 6A8, Canada.); Kitsiou-Tzeli S ( Department of Medical Genetics, Medical School, University of Athens, Athens 11527, Greece.); Rosello M ( Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia 46026, Spain.); Keegan CE ( Department of Pediatrics, Division of Genetics, University of Michigan, Ann Arbor, MI 48109, USA); Lyon GJ ( Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA) |
| Abstract | We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype. Functional analysis with RNA-seq for one of the families suggested that the phenotype is associated with downregulation of a set of genes notably enriched with genes regulated by E-box proteins. In addition, knockdown and mutant studies of this gene in zebrafish have shown a quantifiable, albeit small, effect on a neuronal phenotype. Our results suggest that mutations in TAF1 play a critical role in the development of this X-linked ID syndrome. |
| ISSN | 00029297 |
| e-ISSN | 15376605 |
| DOI | 10.1016/j.ajhg.2015.11.005 |
| Journal | The American Journal of Human Genetics |
| Issue Number | 6 |
| Volume Number | 97 |
| Language | English |
| Publisher | Cell Press (on behalf of American Society of Human Genetics) |
| Publisher Date | 2015-12-03 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Developmental Disabilities Genetics Histone Acetyltransferases Intellectual Disability Neurodegenerative Diseases Tata-binding Protein Associated Factors Transcription Factor Tfiid Adolescent Animals Child, Preschool Metabolism Pathology Disease Models, Animal E-box Elements Facies Gene Expression Regulation Infant Inheritance Patterns Mutation Pedigree Phenotype Signal Transduction Zebrafish Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Human Genetics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
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