How to Cite this Article: Hannes F, Hammond P, Quarrell O, Fryns J-P, Devriendt K, Vermeesch JR. 2012. A microdeletion proximal of the critical deletion region is associated with mild Wolf–Hirschhorn syndrome. Am J Med Genet Part A. 158A:996–1004.
Article first published online: 21 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 5, pages 996–1004, May 2012
How to Cite
Hannes, F., Hammond, P., Quarrell, O., Fryns, J.-P., Devriendt, K. and Vermeesch, J. R. (2012), A microdeletion proximal of the critical deletion region is associated with mild Wolf–Hirschhorn syndrome. Am. J. Med. Genet., 158A: 996–1004. doi: 10.1002/ajmg.a.35299
The authors report no conflict of interest.
- Issue published online: 18 APR 2012
- Article first published online: 21 MAR 2012
- Manuscript Accepted: 1 FEB 2012
- Manuscript Received: 24 JUN 2011
- Wolf–Hirschhorn syndrome;
- 3D facial analysis;
- Wolf–Hirschhorn critical region
It is generally accepted that the facial phenotype of Wolf–Hirschhorn syndrome is caused by deletions of either Wolf–Hirschhorn critical regions 1 or 2 (WHSCR 1–2). Here, we identify a 432 kb deletion located 600 kb proximal to both WHSCR1–2 in a patient with a WHS facial phenotype. Seven genes are underlying this deletion region including FAM193a, ADD1, NOP14, GRK4, MFSD10, SH3BP2, TNIP2. The clinical diagnosis of WHS facial phenotype was confirmed by 3D facial analysis using dense surface modeling. Our results suggest that the WHSCR1–2 flanking sequence contributes directly or indirectly to the severity of WHS. Sequencing the Wolf–Hirschhorn syndrome candidate 1 and 2 genes did not reveal any mutations. Long range position effects of the deletion that could influence gene expression within the WHSCR were excluded in EBV cell lines derived from patient lymphoblasts. We hypothesize that either (1) this locus harbors regulatory sequences which affect gene expression in the WHSCR1–2 in a defined temporal and spatial developmental window or (2) that this locus is additive to deletions of WHSCR1–2 increasing the phenotypic expression. © 2012 Wiley Periodicals, Inc.