Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1626-1629 |
Number of pages | 4 |
Journal | Human Mutation |
Volume | 33 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2012 |
Keywords
- ALX4
- Craniosynostosis
- Dual luciferase
- Gain-of-function
- Sagittal
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)