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A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals

A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals
A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals
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
England, mutation, time, reveals
0002-9297
653-653
Wilkie, A.O.M.
66a9e87f-c7f6-475e-afd6-2972c22a597f
Elanko, N.
baa64101-c520-4179-8cd1-1b61d912be42
Sibbring, J.S.
a1c2777c-8bd2-4331-a5d5-72aaa9cad704
Metcalfe, K.A.
d080278a-3497-441a-ab86-a7526d34ebec
Clayton-Smith, J.
0d43489e-4266-4b0b-b7fa-bacc180062bd
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Wall, S.A.
495a96b6-ba6f-4b63-a686-da161668196e
Donnai, D.
130e1159-bbf6-4925-9b1c-a129a2168387
Wilkie, A.O.M.
66a9e87f-c7f6-475e-afd6-2972c22a597f
Elanko, N.
baa64101-c520-4179-8cd1-1b61d912be42
Sibbring, J.S.
a1c2777c-8bd2-4331-a5d5-72aaa9cad704
Metcalfe, K.A.
d080278a-3497-441a-ab86-a7526d34ebec
Clayton-Smith, J.
0d43489e-4266-4b0b-b7fa-bacc180062bd
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Wall, S.A.
495a96b6-ba6f-4b63-a686-da161668196e
Donnai, D.
130e1159-bbf6-4925-9b1c-a129a2168387

Wilkie, A.O.M., Elanko, N., Sibbring, J.S., Metcalfe, K.A., Clayton-Smith, J., Temple, I.K., Wall, S.A. and Donnai, D. (2001) A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals. American Journal of Human Genetics, 69 (4), 653-653. (doi:10.1002/humu.1230).

Record type: Article

Abstract

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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Published date: 2001
Keywords: England, mutation, time, reveals
Organisations: Medicine

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Local EPrints ID: 60426
URI: http://eprints.soton.ac.uk/id/eprint/60426
ISSN: 0002-9297
PURE UUID: 0ee71e00-efb2-458a-8794-98e5c85610e8
ORCID for I.K. Temple: ORCID iD orcid.org/0000-0002-6045-1781

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Date deposited: 04 Sep 2008
Last modified: 16 Mar 2024 03:03

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Contributors

Author: A.O.M. Wilkie
Author: N. Elanko
Author: J.S. Sibbring
Author: K.A. Metcalfe
Author: J. Clayton-Smith
Author: I.K. Temple ORCID iD
Author: S.A. Wall
Author: D. Donnai

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