Copy Number Variation Analysis in Single-Suture Craniosynostosis: Multiple Rare Variants Including RUNX2 Duplication in Two Cousins With Metopic Craniosynostosis
2010

Copy Number Variation Analysis in Craniosynostosis

Sample size: 186 publication Evidence: moderate

Author Information

Author(s): Heather C. Mefford, Neil Shafer, Francesca Antonacci, Jesse M. Tsai, Sarah S. Park, Anne V. Hing, Mark J. Rieder, Matthew D. Smyth, Matthew L. Speltz, Evan E. Eichler, Michael L. Cunningham

Primary Institution: University of Washington

Hypothesis

Rare copy number variants (CNV) in patients with isolated single-suture craniosynostosis contain genes important for cranial development.

Conclusion

The study identified a duplication of the RUNX2 gene in two cousins with metopic craniosynostosis, suggesting a pathogenic role in craniosynostosis.

Supporting Evidence

  • 7.5% of individuals with single-suture synostosis had at least one rare deletion or duplication.
  • A 1.1 Mb duplication encompassing RUNX2 was identified in two affected cousins.
  • RUNX2 is required for osteoblast differentiation and is linked to craniosynostosis.
  • Previous studies have shown that mutations in RUNX2 can lead to craniosynostosis.

Takeaway

The researchers looked at DNA from kids with a head shape problem and found some changes in their genes that might help explain why they have this issue.

Methodology

Whole genome array comparative genomic hybridization (CGH) was used to evaluate DNA for submicroscopic deletions and duplications.

Limitations

The study was limited by the availability of parental DNA for some cases, which restricted inheritance analysis.

Participant Demographics

Participants included individuals with isolated single-suture craniosynostosis, aged ≤30 months at enrollment.

Statistical Information

P-Value

0.036

Statistical Significance

p=0.036

Digital Object Identifier (DOI)

10.1002/ajmg.a.33557

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