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Mutations in the human TWIST gene
Author(s) -
Gripp Karen W.,
Zackai Elaine H.,
Stolle Catherine A.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200002)15:2<150::aid-humu3>3.0.co;2-d
Subject(s) - haploinsufficiency , biology , genetics , missense mutation , gene , nonsense , nonsense mutation , twist transcription factor , point mutation , mutation , phenotype , transcription factor , nuclear protein
Saethre‐Chotzen syndrome is a relatively common craniosynostosis disorder with autosomal dominant inheritance. Mutations in the TWIST gene have been identified in patients with Saethre‐Chotzen syndrome. The TWIST gene product is a transcription factor with DNA binding and helix‐loop‐helix domains. Numerous 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 disabilities or mental retardation, which are not typically part of the Saethre‐Chotzen syndrome. Comprehensive studies in patients with the clinical diagnosis 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 haploinsufficiency as the disease‐causing mechanism. No genotype phenotype correlation was apparent. Hum Mutat 15:150–155, 2000. © 2000 Wiley‐Liss, Inc.