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Functional analysis of natural mutations in two TWIST protein motifs

2005; Wiley; Volume: 25; Issue: 6 Linguagem: Inglês

10.1002/humu.20176

1098-1004

Noriko Funato, Stephen R.F. Twigg, Norihisa Higashihori, Kimie Ohyama, Steven A. Wall, Andrew O.M. Wilkie, Masataka Nakamura,

Genomics and Rare Diseases

Human MutationVolume 25, Issue 6 p. 550-556 Research Article Functional analysis of natural mutations in two TWIST protein motifs† Noriko Funato, Noriko Funato Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, JapanSearch for more papers by this authorStephen R.F. Twigg, Stephen R.F. Twigg Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Laboratory Services (NDCLS), University of Oxford, Oxford, United KingdomSearch for more papers by this authorNorihisa Higashihori, Norihisa Higashihori Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, JapanSearch for more papers by this authorKimie Ohyama, Kimie Ohyama Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, JapanSearch for more papers by this authorSteven A. Wall, Steven A. Wall Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford, United KingdomSearch for more papers by this authorAndrew O.M. Wilkie, Corresponding Author Andrew O.M. Wilkie [email protected] Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Laboratory Services (NDCLS), University of Oxford, Oxford, United Kingdom Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford, United Kingdom Andrew O.M. Wilkie, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom Masataka Nakamura, Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, JapanSearch for more papers by this authorMasataka Nakamura, Corresponding Author Masataka Nakamura [email protected] Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan Andrew O.M. Wilkie, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom Masataka Nakamura, Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, JapanSearch for more papers by this author Noriko Funato, Noriko Funato Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, JapanSearch for more papers by this authorStephen R.F. Twigg, Stephen R.F. Twigg Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Laboratory Services (NDCLS), University of Oxford, Oxford, United KingdomSearch for more papers by this authorNorihisa Higashihori, Norihisa Higashihori Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, JapanSearch for more papers by this authorKimie Ohyama, Kimie Ohyama Maxillofacial Orthognathics, Tokyo Medical and Dental University, Tokyo, JapanSearch for more papers by this authorSteven A. Wall, Steven A. Wall Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford, United KingdomSearch for more papers by this authorAndrew O.M. Wilkie, Corresponding Author Andrew O.M. Wilkie [email protected] Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Laboratory Services (NDCLS), University of Oxford, Oxford, United Kingdom Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford, United Kingdom Andrew O.M. Wilkie, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom Masataka Nakamura, Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, JapanSearch for more papers by this authorMasataka Nakamura, Corresponding Author Masataka Nakamura [email protected] Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan Andrew O.M. Wilkie, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom Masataka Nakamura, Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, JapanSearch for more papers by this author First published: 10 May 2005 https://doi.org/10.1002/humu.20176Citations: 15 † Communicated by Haig H. Kazazian AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The basic helix-loop-helix protein Twist, a transcriptional repressor, is essential for embryogenesis in both invertebrates and vertebrates. Haploinsufficiency of the human TWIST1 gene, which causes the craniosynostosis disorder Saethre-Chotzen syndrome (SCS), is related to failure to repress transcription of CDKN1A (which encodes p21/WAF1/CIP1), promoting osteoblast differentiation. We have examined the functional significance of natural TWIST1 variants present in craniosynostosis patients and in their healthy relatives. Both deletion and duplication variants of the glycine-rich tract Gly5AlaGly5 inhibited E2A (E12/E47)-dependent transcription of CDKN1A to a similar degree as wild-type protein, indicating that the length of this glycine tract is not critical for efficient transcriptional repression. We also evaluated a newly identified heterozygous TWIST1 variant (c.115C>G, encoding p.Arg39Gly), located within a putative nuclear localization signal (NLS), that was present in a child with mild SCS and her clinically unaffected father and grandmother. 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The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes. Dev Biol 143: 363– 373. Citing Literature Volume25, Issue6June 2005Pages 550-556 ReferencesRelatedInformation