Saethre-Chotzen syndrome is one of the most common autosomal dominant disorders 
of craniosynostosis in humans and is characterized by craniofacial and limb 
anomalies. The locus for Saethre-Chotzen syndrome maps to chromosome 7p21-p22. 
We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a 
candidate gene for this condition because its expression pattern and mutant 
phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen 
phenotype. We mapped TWIST to human chromosome 7p21-p22 and mutational analysis 
reveals nonsense, missense, insertion and deletion mutations in patients. These 
mutations occur within the basic DNA binding, helix I and loop domains, or 
result in premature termination of the protein. Studies in Drosophila indicate 
that twist may affect the transcription of fibroblast growth factor receptors 
(FGFRs), another gene family implicated in human craniosynostosis. The emerging 
cascade of molecular components involved in craniofacial and limb development 
now includes TWIST, which may function as an upstream regulator of FGFRs.