Translocation breakpoint maps 5 kb 3' from TWIST in a patient affected with Saethre-Chotzen syndrome

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 similar to 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.