X-linked congenital ptosis and associated intellectual disability,short stature,microcephaly, cleft palate,digital and genital abnormalities define novel Xq25q26 duplication syndrome |
| |
Authors: | R. S. Møller L. R. Jensen S. M. Maas J. Filmus M. Capurro C. Hansen C. L. M. Marcelis K. Ravn J. Andrieux M. Mathieu M. Kirchhoff O. K. Rødningen N. de Leeuw H. G. Yntema G. Froyen J. Vandewalle K. Ballon E. Klopocki S. Joss J. Tolmie A. C. Knegt A. M. Lund H. Hjalgrim A. W. Kuss N. Tommerup R. Ullmann A. P. M. de Brouwer P. Strømme S. Kjaergaard Z. Tümer T. Kleefstra |
| |
Affiliation: | 1. Danish Epilepsy Centre, Dianalund, Kolonivej 7, 4293, Dianalund, Denmark 18. Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark 2. Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark 22. Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University, Greifswald, Germany 3. Institute for Human Genetics, University Medicine Greifswald, Greifswald, Germany 4. Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands 5. Department of Paediatrics, Academic Medical Center, Amsterdam, The Netherlands 6. Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada 7. Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands 8. Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet Gl. Landevej 7, 2600, Glostrup, Denmark 9. Institut de Génétique Médicale, Hopital Jeanne de Flandre, CHRU, Lille, France 10. Service de Génétique Clinique, CHU d’Amiens, Amiens, France 11. Department of Clinical Genetics, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark 12. Department of Medical Genetics, Oslo University Hospital, Ullevaal, Norway 13. Human Genome Laboratory, Department of Human Genetics, VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium 14. Department of Paediatrics, University Hospitals Leuven, Louvain, Belgium 15. Institute for Medical and Human Genetics, Charité Universit?tsmedizin Berlin, Berlin, Germany 16. Institute for Human Genetics, University of Würzburg, Würzburg, Germany 17. Ferguson-Smith Department of Clinical Genetics, Yorkhill Hospital, Glasgow, UK 19. Max Planck Institute for Molecular Genetics, Berlin, Germany 20. Department of Cognitive Neurosciences, Donders Institute for Brain Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands 21. Women and Children’s Division, Department of Clinical Neurosciences for Children, University Hospital and University of Oslo, Oslo, Norway
|
| |
Abstract: | Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|