FOXL2 copy number changes in the molecular pathogenesis of BPES: unique cohort of 17 deletions |
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| Authors: | B. D'haene J. Nevado M. Pugeat G. Pierquin R.B. Lowry W. Reardon A. Delicado S. García‐Miñaur M. Palomares W. Courtens M. Stefanova S. Wallace W. Watkins A. N. Shelling D. Wieczorek R. A. Veitia A. De Paepe P. Lapunzina E. De Baere |
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| Affiliation: | 1. Center for Medical Genetics, Ghent University Hospital, Belgium;2. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, CIBERER, U783‐ISCIII, Spain;3. Department of Endocrinology, East Pole of Lyon Hospitals and INSERM Unit 0322, Lyon, France;4. Center for Human Genetics, CHU Sart‐Tilman, University of Liège, Liège, Belgium;5. Department of Medical Genetics, Alberta Children's Hospital, Alberta, Calgary, Canada;6. National Centre for Medical Genetics, Our Lady's Hospital for Sick Children, Dublin, Ireland;7. Center of Human Genetics UCL, Cliniques Universitaires St‐Luc Brussels, Brussels, Belgium;8. Department of Clinical Genetics, Sahlgrenska University Hospital, G?teborg, Sweden;9. Division of Genetics and Developmental Medicine, University of Washington, Washington, United States;10. Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;11. Institut für Humangenetik, Universit?tsklinikum, Essen, Germany;12. UMR7592‐CNRS, Institut Jacques Monod, Paris, France;13. Université Denis Diderot, Paris VII, Paris, France |
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| Abstract: | Blepharophimosis Syndrome (BPES) is an autosomal dominant developmental disorder of the eyelids with or without ovarian dysfunction caused by FOXL2 mutations. Overall, FOXL2deletions represent 12% of all genetic defects in BPES. Here, we have identified and characterized 16 new and one known FOXL2 deletion combining multiplex ligation‐dependent probe amplification (MLPA), custom‐made quantitative PCR (qPCR) and/or microarray‐based copy number screening. The deletion breakpoints could be localized for 13 out of 17 deletions. The deletion size is highly variable (29.8 kb ‐ 11.5 Mb), indicating absence of a recombination hotspot. Although the heterogeneity of their size and breakpoints is not reflected in the uniform BPES phenotype, there is considerable phenotypic variability regarding associated clinical findings including psychomotor retardation (8/17), microcephaly (6/17), and subtle skeletal features (2/17). In addition, in all females in whom ovarian function could be assessed, FOXL2 deletions proved to be associated with variable degrees of ovarian dysfunction. In conclusion, we present the largest series of BPES patients with FOXL2 deletions and standardized phenotyping reported so far. Our genotype‐phenotype data can be useful for providing a prognosis (i.e. occurrence of associated features) in newborns with BPES carrying a FOXL2 deletion. © 2010 Wiley‐Liss, Inc. |
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| Keywords: | FOXL2 BPES gene deletion genotype‐phenotype correlations |
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