A MUTATION IN THE HOMEODOMAIN OF THE HUMAN MSX2 GENE IN A FAMILY AFFECTED WITH AUTOSOMAL-DOMINANT CRANIOSYNOSTOSIS

Craniosynostosis, the premature fusion of calvarial sutures, is a comm on developmental anomaly that causes abnormal skull shape. The locus f or one autosomal dominant form of craniosynostosis has been mapped to chromosome 5qter. The human MSX2 gene localizes to chromosome 5, and a polymorphic marker in the MSX2 intron segregates in a kindred with th e disorder with no recombination. Moreover, a histidine substitutes fo r a highly conserved proline at position 7 of the MSX2 homeodomain exc lusively in affected members. In the mouse, transcripts of the Msx2 ge ne are localized to calvarial sutures. These results provide compellin g evidence that the mutation causes this craniosynostosis syndrome.