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De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder
Authors:Margot RF Reijnders  Kerry A Miller  Mohsan Alvi  Jacqueline AC Goos  Melissa M Lees  Anna de Burca  Alex Henderson  Alison Kraus  Barbara Mikat  Bert BA de Vries  Bertrand Isidor  Bronwyn Kerr  Carlo Marcelis  Caroline Schluth-Bolard  Charu Deshpande  Claudia AL Ruivenkamp  Dagmar Wieczorek  Andrew OM Wilkie
Institution:1. Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, 6500 HB, the Netherlands;2. Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK;3. Visual Geometry Group, Department of Engineering Science, University of Oxford, Oxford OX1 2JD, UK;4. Department of Plastic and Reconstructive Surgery, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands;5. Department of Clinical Genetics, Great Ormond Street Hospital, London WC1N 3JH, UK;6. Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE, UK;7. Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 3BZ, UK;8. Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds LS7 4SA, UK;9. Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, 45147 Essen, Germany;10. CHU de Nantes, Service de Génétique Médicale, Nantes 44093 Cedex 1, France;11. INSERM, UMR-S 957, 1 Rue Gaston Veil, Nantes 44035, France;12. Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK;13. Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9WL, UK;14. Department of Human Genetics, Radboud University Medical Center, Nijmegen 6500 HB, the Netherlands;15. Hospices Civils de Lyon, Service de Génétique, Centre de Référence Anomalies du Développement, 69500 Bron, France;16. INSERM U1028, CNRS UMR5292, UCB Lyon 1, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, 69500 Bron, France;17. South East Thames Regional Genetics Service, Guy’s Hospital, London SE1 9RT, UK;18. Department of Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands;19. Institute of Human Genetics, Heinrich-Heine-University, Medical Faculty, 40225 Düsseldorf, Germany;20. Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK;21. Human Development and Health, Duthie Building, University of Southampton, Southampton SO16 6YD, UK;22. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK;23. Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, 53127 Bonn, Germany;24. Nottingham Regional Genetics Service, City Hospital Campus, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham NG5 1PB, UK;25. Southwest Thames Regional Genetics Centre, St George’s University Hospitals NHS Foundation Trust, St George’s University of London, London SW17 0RE, UK;26. Riley Hospital for Children, Indianapolis, Indiana, IN 46202, USA;27. Division of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA 92656, USA;28. Department of Pediatrics, Baylor College of Medicine, The Children’s Hospital of San Antonio, San Antonio, TX 78207, USA;29. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;30. Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;31. Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany;32. University of California, San Diego, Department of Pediatrics; Genetics and Dysmorphology, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA;33. Department of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, Maastricht 6229 ER, the Netherlands;34. Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK;35. Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 21455, 3001 AL Rotterdam, the Netherlands;36. Department of Clinical Genetics, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, the Netherlands;37. Department of Genetics, University Medical Center Utrecht, 3508 AB Utrecht, the Netherlands;38. Division of Genetics, Department of Pediatrics, McMaster Children’s Hospital, McMaster University, Hamilton, ON L8N 3Z5, Canada;39. Department of Paediatrics, Maastricht University Medical Center, Maastricht 6229 ER, the Netherlands;40. Department of Medical Genetics, University of British Columbia, Vancouver, BC V8Z 6R5, Canada;41. West Midlands Regional Clinical Genetics Unit, Birmingham Women’s & Children’s NHS Foundation Trust, Mindelsohn Way, Birmingham B15 2TG, UK;42. Genetic Health Service New Zealand, Auckland 1142, New Zealand;43. Victorian Clinical Genetic Services, Murdoch Children’s Research Institute, Melbourne, VIC 3052, Australia;44. University of Auckland, Auckland 1142, New Zealand;45. Department of Pathology & Department of Bioinformatics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands;46. Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, Toronto, ON, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5G 1X8, Canada;47. West of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK;48. Craniofacial Unit, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK;49. CHU de Nantes, Service de Génétique Médicale, 44093 Nantes Cedex 1, France;50. Computational Biology Research Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK;51. Nuffield Department of Women’s and Reproductive Health, University of Oxford, Women’s Centre, John Radcliffe Hospital, Oxford OX3 9DS, UK;52. Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX3 7FZ, UK;53. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK
Abstract:
Keywords:Tousled-like  kinase  haploinsufficiency  facial averaging  intellectual disability
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