Communicated by Maria Rita Passos-Bueno
ALX4 gain-of-function mutations in nonsyndromic craniosynostosis†
Article first published online: 13 AUG 2012
© 2012 Wiley Periodicals, Inc.
Volume 33, Issue 12, pages 1626–1629, December 2012
How to Cite
Yagnik, G., Ghuman, A., Kim, S., Stevens, C. G., Kimonis, V., Stoler, J., Sanchez-Lara, P. A., Bernstein, J. A., Naydenov, C., Drissi, H., Cunningham, M. L., Kim, J. and Boyadjiev, S. A. (2012), ALX4 gain-of-function mutations in nonsyndromic craniosynostosis. Hum. Mutat., 33: 1626–1629. doi: 10.1002/humu.22166
- Issue published online: 12 NOV 2012
- Article first published online: 13 AUG 2012
- Accepted manuscript online: 24 JUL 2012 09:11AM EST
- Manuscript Accepted: 3 JUL 2012
- Manuscript Received: 2 APR 2012
- Children's Miracle Network Endowed Chair (to S.A.B.)
- NIDCR/NIH. Grant Numbers: K23 DE00462, R03 DE016342, and R01 DE016886 [to S.A.B.], 3R37DE012711-13S1 and K12-HD05954 [to P.A.S-L])
- Harold Amos Faculty Development Program through the RWJ Foundation [to P.A.S-L] and R01 DE018227 [to M.L.C.])
- NCRR/NIH. Grant Number: M01-RR00052 to S.A.B.
- dual luciferase
Craniosynostosis is the early fusion of one or more sutures of the infant skull and is a common defect occurring in approximately 1 of every 2,500 live births. Nonsyndromic craniosynostosis (NSC) accounts for approximately 80% of all cases and is thought to have strong genetic determinants that are yet to be identified. ALX4 is a homeodomain transcription factor with known involvement in osteoblast regulation. By direct sequencing of the ALX4 coding region in sagittal or sagittal-suture-involved nonsyndromic craniosynostosis probands, we identified novel, nonsynonymous, familial variants in three of 203 individuals with NSC. Using dual-luciferase assay we show that two of these variants (V7F and K211E) confer a significant gain-of-function effect on ALX4. Our results suggest that ALX4 variants may have an impact on the genetic etiology of NSC. Hum Mutat 33:1626–1629, 2012. © 2012 Wiley Periodicals, Inc.