ALX4 gain-of-function mutations in nonsyndromic craniosynostosis

Garima Yagnik, Apar Ghuman, Sundon Kim, Christina G. Stevens, Virginia Kimonis, Joan Stoler, Pedro A. Sanchez-Lara, Jonathan A. Bernstein, Cyril Naydenov, Hicham Drissi, Michael L. Cunningham, Jinoh Kim, Simeon Boyd

Research output: Contribution to journalArticle

13 Scopus citations


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 languageEnglish (US)
Pages (from-to)1626-1629
Number of pages4
JournalHuman Mutation
Issue number12
StatePublished - Dec 2012


  • ALX4
  • Craniosynostosis
  • Dual luciferase
  • Gain-of-function
  • Sagittal

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    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., & Boyd, S. (2012). ALX4 gain-of-function mutations in nonsyndromic craniosynostosis. Human Mutation, 33(12), 1626-1629.