A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis

EW Jabs, U Müller, X Li, L Ma, W Luo, IS Haworth… - Cell, 1993 - cell.com
EW Jabs, U Müller, X Li, L Ma, W Luo, IS Haworth, I Klisak, R Sparkes, ML Warman…
Cell, 1993cell.com
Craniosynostosis, the premature fusion of calvarial sutures, is a common developmental
anomaly that causes abnormal skull shape. The locus for one autosomal dominant form of
craniosynostosis has been mapped to chromosome Bqter. The human MSX2 gene localizes
to chromosome 5, and a polymorphic marker in the MSX2 intron segregates in a kindred
with the disorder with no recombination. Moreover, a histidine substitutes for a highly
conserved proline at position 7 of the MSXP homeodomain exclusively in affected members …
Summary
Craniosynostosis, the premature fusion of calvarial sutures, is a common developmental anomaly that causes abnormal skull shape. The locus for one autosomal dominant form of craniosynostosis has been mapped to chromosome Bqter. The human MSX2 gene localizes to chromosome 5, and a polymorphic marker in the MSX2 intron segregates in a kindred with the disorder with no recombination. Moreover, a histidine substitutes for a highly conserved proline at position 7 of the MSXP homeodomain exclusively in affected members. In the mouse, transcripts of the MsxP gene are localized to calvarial sutures. These results provide compelling evidence that the mutation causes this craniosynostosis syndrome.
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