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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.
twist, saethre-chotzen syndrome, scs, craniosynostosis, polyglycine, triplet repeat, bHLH
1059-7794
535-541
Elanko, Navaratnam
7839576b-005d-4f7e-b6eb-93ad588d1934
Sibbring, Julie S.
26dd4405-5654-43be-acd1-2fc4abcec58e
Metcalfe, Kay A.
8230b4bf-027d-4580-9248-3a8864c8d601
Clayton-Smith, Jill
df8946ac-9da9-4ef2-b180-f468a5424844
Donnai, Dian
7758b3a7-e2ea-4330-8c72-fdf6d4e75eea
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Wall, Steven A.
cb2e3e72-4c66-48b6-98a5-f03222aedaf1
Wilkie, Andrew O.M.
7064a09e-66d9-4acf-92eb-cffad1ce3762
Elanko, Navaratnam
7839576b-005d-4f7e-b6eb-93ad588d1934
Sibbring, Julie S.
26dd4405-5654-43be-acd1-2fc4abcec58e
Metcalfe, Kay A.
8230b4bf-027d-4580-9248-3a8864c8d601
Clayton-Smith, Jill
df8946ac-9da9-4ef2-b180-f468a5424844
Donnai, Dian
7758b3a7-e2ea-4330-8c72-fdf6d4e75eea
Temple, I. Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Wall, Steven A.
cb2e3e72-4c66-48b6-98a5-f03222aedaf1
Wilkie, Andrew O.M.
7064a09e-66d9-4acf-92eb-cffad1ce3762

Elanko, Navaratnam, Sibbring, Julie S., Metcalfe, Kay A., Clayton-Smith, Jill, Donnai, Dian, Temple, I. Karen, Wall, Steven A. and Wilkie, Andrew O.M. (2001) A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals. Human Mutation, 18 (6), 535-541. (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: December 2001
Keywords: twist, saethre-chotzen syndrome, scs, craniosynostosis, polyglycine, triplet repeat, bHLH
Organisations: Human Genetics

Identifiers

Local EPrints ID: 24690
URI: https://eprints.soton.ac.uk/id/eprint/24690
ISSN: 1059-7794
PURE UUID: 2711816e-dc52-4ef8-954b-737e8ff368fb
ORCID for I. Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781

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Date deposited: 03 Apr 2006
Last modified: 20 Jul 2019 01:10

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Contributors

Author: Navaratnam Elanko
Author: Julie S. Sibbring
Author: Kay A. Metcalfe
Author: Jill Clayton-Smith
Author: Dian Donnai
Author: I. Karen Temple ORCID iD
Author: Steven A. Wall
Author: Andrew O.M. Wilkie

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