A survey ofTWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals
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The human TWIST gene encodes a 202 amino acid transcription factor characterized by a highly conserved basic-helix-loop-helix motif in the C-terminal half, and a less conserved N-terminal half that has binding activity toward the histone acetyltransferase p300. Between these domains is a repeat region of unknown function that encodes the glycine-rich sequence (Gly)5Ala(Gly)5. Heterozygous mutations of TWIST were previously described in Saethre-Chotzen craniosynostosis syndrome [El Ghouzzi et al., 1997; Howard et al., 1997]. During a search for TWIST mutations in patients with craniosynostosis, we identified, in addition to 11 novel and one previously described bona fide mutations, several individuals with rearrangements of the glycine-rich region, involving either deletion of 18 nucleotides or insertion of three, 15, or 21 nucleotides. None of these rearrangements was consistently associated with clinical disease and we conclude that they are at most weakly pathogenic. The glycine stretch may serve as a flexible linker between the functional domains of the TWIST protein, and as such may be subject to reduced evolutionary constraint.
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Rearrangements of a polyglycine-rich tract (amino acids 82-92) appear harmless in the heterozygous state.
“Rearrangements of a polyglycine-rich tract (amino acids 82-92), which turn up occasionally during mutation screening, seem to be harmless in the heterozygous state.29”
From Craniosynostosis (2011) · cites this paper as [29]
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- Authors
- Elanko, N., Sibbring, J. S., Metcalfe, K. A., Clayton-Smith, J., Donnai, D., Temple, I. K., Wall, S. A., & Wilkie, A. O. M.
- Affiliations
- University of Oxford (GB)
- St Mary's Hospital (GB)
- Princess Anne Hospital (GB)
- John Radcliffe Hospital (GB)
- Corresponding author
- Wilkie, Andrew O.M.
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2001
- Volume
- 18
- Issue
- 6
- Pages
- 535-541
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2151601827
- Cited by
- 41
- References
- 29
- Citations by year
- 2024: 1 · 2020: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 4
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- twist gene, craniosynostosis, Saethre-Chotzen syndrome, glycine-rich region, heterozygous mutation, bHLH transcription factors, asymptomatic carriers, novel mutations, insertion-deletion variants, evolutionary constraints
- MeSH terms
- Amino Acid Sequence, Base Sequence, Craniosynostoses, DNA, DNA Mutational Analysis, Family Health, Female, Genetic Testing, Humans, Male, Molecular Sequence Data, Mutation, Nuclear Proteins, Pedigree, Peptides, Sequence Homology, Nucleic Acid, Transcription Factors, Genetic Variation, Mutagenesis, Insertional, Sequence Deletion, Sequence Homology, Amino Acid, Twist-Related Protein 1
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