Saethre-Chotzen syndrome, a common autosomal dominant craniosynostosis in 
humans, is characterized by brachydactyly, soft tissue syndactyly and facial 
dysmorphism including ptosis, facial asymmetry, and prominent ear crura. 
Previously, we identified a yeast artificial chromosome that encompassed the 
breakpoint of an apparently balanced t(6;7) (q16.2;p15.3) translocation 
associated with a mild form of Saethre-Chotzen syndrome. We now describe, at the 
DNA sequence level, the region on chromosome 7 affected by this translocation 
event. The rearrangement occurred approximately 5 kb 3' of the human TWIST locus 
and deleted 518 bp of chromosome 7. The TWIST gene codes for a transcription 
factor containing a basic helix-loop-helix (b-HLH) motif and has recently been 
described as a candidate gene for Saethre-Chotzen syndrome, based on the 
detection of mutations within the coding region. Potential exon sequences 
flanking the chromosome 7 translocation breakpoint did not hit known genes in 
database searches. The chromosome rearrangement downstream of TWIST is 
compatible with the notion that this is a Saethre-Chotzen syndrome gene and 
implies loss of function of one allele by a positional effect as a possible 
mechanism of mutation to evoke the syndrome.