Deletions of the RUNX2 gene are present in about 10% of individuals with cleidocranial dysplasia |
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| Authors: | Claus E. Ott Gundula Leschik Fabienne Trotier Louise Brueton Han G. Brunner Wim Brussel Encarna Guillen‐Navarro Claudia Haase Juergen Kohlhase Dieter Kotzot Andrew Lane Min Ae Lee‐Kirsch Susanne Morlot Marleen E.H. Simon Elisabeth Steichen‐Gersdorf David H. Tegay Hartmut Peters Stefan Mundlos Eva Klopocki |
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| Affiliation: | 1. Institut für Medizinische Genetik, Charité‐Universit?tsmedizin Berlin, Berlin, Germany;2. Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, United Kingdom;3. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;4. Department of Pediatrics, Hospital Rijnstate Arnhem, Arnhem, The Netherlands;5. Unit of Medical Genetics, Department of Pediatrics, Virgen de la Arrixaca University Hospital, Murcia, Spain;6. Department of Pediatrics, University of Jena, Jena, Germany;7. Praxis für Humangenetik, Freiburg, Germany;8. Division of Clinical Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria;9. Department of Pediatrics, Stony Brook University Medical Center, Stony Brook, NY, USA;10. Klinik für Kinder‐ und Jugendmedizin, Technische Universit?t Dresden, Dresden, Germany;11. Praxis für Humangenetik, MVZ wagnerstibbe, Hannover, Germany;12. Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands;13. Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria;14. Department of Medicine, New York College of Osteopathic Medicine, Old Westbury, NY, USA;15. Max Planck Institut für Molekulare Genetik, Berlin, Germany |
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| Abstract: | Cleidocranial Dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by hypoplastic or absent clavicles, increased head circumference, large fontanels, dental anomalies, and short stature. Hand malformations are also common. Mutations in RUNX2 cause CCD, but are not identified in all CCD patients. In this study we screened 135 unrelated patients with the clinical diagnosis of CCD for RUNX2 mutations by sequencing analysis and demonstrated 82 mutations 48 of which were novel. By quantitative PCR we screened the remaining 53 unrelated patients for copy number variations in the RUNX2 gene. Heterozygous deletions of different size were identified in 13 patients, and a duplication of the exons 1 to 4 of the RUNX2 gene in one patient. Thus, heterozygous deletions or duplications affecting the RUNX2 gene may be present in about 10% of all patients with a clinical diagnosis of CCD which corresponds to 26% of individuals with normal results on sequencing analysis. We therefore suggest that screening for intragenic deletions and duplications by qPCR or MLPA should be considered for patients with CCD phenotype in whom DNA sequencing does not reveal a causative RUNX2 mutation. © 2010 Wiley‐Liss, Inc. |
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