Communicated by Iain McIntosh
Mutation in Brief
FOXL2 copy number changes in the molecular pathogenesis of BPES: unique cohort of 17 deletions†
Article first published online: 15 MAR 2010
© 2010 Wiley-Liss, Inc.
Volume 31, Issue 5, pages E1332–E1347, May 2010
How to Cite
D'haene, B., Nevado, J., Pugeat, M., Pierquin, G., Lowry, R.B., Reardon, W., Delicado, A., García-Miñaur, S., Palomares, M., Courtens, W., Stefanova, M., Wallace, S., Watkins, W., Shelling, A. N., Wieczorek, D., Veitia, R. A., De Paepe, A., Lapunzina, P. and De Baere, E. (2010), FOXL2 copy number changes in the molecular pathogenesis of BPES: unique cohort of 17 deletions. Hum. Mutat., 31: E1332–E1347. doi: 10.1002/humu.21233
- Issue published online: 29 APR 2010
- Article first published online: 15 MAR 2010
- Manuscript Accepted: 17 FEB 2010
- Manuscript Received: 16 NOV 2009
- Cited By
- gene deletion;
- genotype-phenotype correlations
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.