Heterozygous Mutations of FREM1 Are Associated with an Increased Risk of Isolated Metopic Craniosynostosis in Humans and Mice

2011

FREM1 Mutations Linked to Metopic Craniosynostosis

Sample size: 109 publication 10 minutes Evidence: high

Author Information

Author(s): Vissers Lisenka E. L. M., Cox Timothy C., Maga A. Murat, Short Kieran M., Wiradjaja Fenny, Janssen Irene M., Jehee Fernanda, Bertola Debora, Liu Jia, Yagnik Garima, Sekiguchi Kiyotoshi, Kiyozumi Daiji, van Bokhoven Hans, Marcelis Carlo, Cunningham Michael L., Anderson Peter J., Boyadjiev Simeon A., Passos-Bueno Maria Rita, Veltman Joris A., Smyth Ian, Buckley Michael F., Roscioli Tony

Primary Institution: Radboud University Nijmegen Medical Centre

Hypothesis

Are heterozygous mutations of FREM1 associated with an increased risk of isolated metopic craniosynostosis in humans and mice?

Conclusion

Mutations in FREM1 are associated with trigonocephaly and can lead to craniofacial abnormalities.

Supporting Evidence

Five CNVs involving FREM1 were identified in patients with metopic craniosynostosis.
Mouse models showed advanced fusion of the metopic suture in homozygous mutants.
FREM1 mutations were found to be de novo in several patients.
Expression of FREM1 was observed in the developing frontal and nasal sutures in mice.
Clinical features of trigonocephaly were noted in patients with FREM1 mutations.

Takeaway

This study found that changes in a specific gene called FREM1 can cause a condition where a baby's forehead bones fuse too early, leading to an unusual head shape.