Mutations in the human TWIST gene

Saethre-Chotzen syndrome is a relatively common craniosynostosis disorder w ith autosomal dominant inheritance. Mutations in the TWIST gene have been i dentified in patients with Saethre-Chotzen syndrome. The TWIST gene product is a transcription factor with DNA binding and helix-loop helix domains. N umerous missense and nonsense mutations cluster in the functional domains, without any apparent mutational hot spot. Two novel point mutations and one novel polymorphism are included in this review. Large deletions including the TWIST gene have been identified in some patients with learning disabili ties or mental retardation, which are not typically part of the Saethre-Cho tzen syndrome. Comprehensive studies in patients with the clinical diagnosi s of Saethre-Chotzen syndrome have demonstrated a TWIST gene abnormality in about 80%, up to 37% of which may be large deletions [Johnson et al., 1998 ]. The gene deletions and numerous nonsense mutations are suggestive of hap loinsufficiency as the disease-causing mechanism, No genotype phenotype cor relation was apparent. Hum Mutat 15:150-155, 2000. (C) 2000 Wiley-Liss, Inc .