Heterozygous Mutations of FREM1 Are Associated with an Increased Risk of Isolated Metopic Craniosynostosis in Humans and Mice
Figure 5
Frem1bat and Frem1Qbrick mice exhibit advanced posterior frontal suture fusion.
Rendered 3D images of postnatal day 28 heads were generated from microcomputed tomographic scan data and each virtually sectioned in the coronal plane at the same position through the posterior frontal suture (i – dorsal view of position of coronal plane; ii – frontal view of rendered image in (i)). The region indicated by the rectangle is shown in (iii) for a control (+/+) skull, homozygote Frem1bat (bat/bat) and Frem1Qbrick (qb/qb) skulls, as well as different heterozygote Frem1bat (bat/+) and Frem1Qbrick (qb/qb) skulls. The most severely affected heterozygote Frem1bat (bat/+) posterior frontal suture is also shown. Control skulls all showed sparse points of contact (typically just on the endocranial surface) between the frontal bones, indicative of the early stages of suture fusion. Fusion of the posterior frontal suture is largely completed by ∼postnatal day 45 in controls. In contrast, the Frem1bat/bat and Frem1qb/qb skulls exhibited extensive fusion both on the endocranial and ectocranial surfaces (arrowheads) at day 28, indicating advanced fusion of this suture. Heterozygotes also showed variable suture anomalies, from complete fusion to asymmetry of the suture.