THE TWIST GENE, ALTHOUGH NOT DISRUPTED IN SAETHRE-CHOTZEN PATIENTS WITH APPARENTLY BALANCED TRANSLOCATIONS OF 7P21, IS MUTATED IN FAMILIAL AND SPORADIC CASES

The TWIST gene maps to 7p21 and mutations in the gene have been report ed in the Saethre-Chotzen form of craniosynostosis, The position of th e Saethre-Chotzen gene has previously been refined by FISH analysis of four patients carrying balanced translocations involving 7p21 which s uggested that it was located between D7S488 and D7S503, We report here that the breakpoints in four translocation patients do not interrupt the coding sequence of the TWIST gene and thus most likely act through a positional effect, Twelve Saethre-Chotzen cases were found to have TWIST mutations. Four of these families had been used as part of the l inkage study of the Saethre-Chotzen locus, The mutations detected incl uded missense and nonsense mutations and three cases of a 21 bp duplic ation. Although phenotypically diagnosed as having Saethre-Chotzen syn drome, three families were found to have a pro250arg mutation of FGFR3 .