Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes
| العنوان: | Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes |
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| المؤلفون: | Elise Valkanas, Hon-Yin Brian Chung, Peter Farndon, Patricia M. Zerfas, Oliver Bartsch, Martin Zenker, Jeroen Bakkers, Alexander Hoischen, Feliciano J. Ramos, Eva Bermejo-Sánchez, Haigen Huang, Gijs van Haaften, Lynne A. Wolfe, Taylor Davis, Eduarda Morgana da Silva, Han G. Brunner, W. K. Jacyk, Bruno Dallapiccola, Laura Mazzanti, Cathy A. Stevens, Mieke M. van Haelst, Hanka Venselaar, Cornelius F. Boerkoel, Francesco Brancati, Cynthia J. Tifft, May Christine V. Malicdan, Nathalie Roche, Bert B.A. de Vries, Victor Evangelista de Faria Ferraz, Chyi-Chia Richard Lee, Brian P. Brooks, Farahnaz Sabbagh-Kermani, Federico Tessadori, Denny Schanze, Barbara N. Pusey, Ariana Kariminejad, Valerie Maduro, Janice Lee, Giovanna Zambruno, Shuo Lin, Cédric Le Caignec, Thomas C. Markello, Maria Tsokos, Shannon Marchegiani, Fabiana Martins, William A. Gahl, Anneke T. Vulto-van Silfhout |
| المساهمون: | Other departments, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Marchegiani, Shannon, Davis, Taylor, Tessadori, Federico, Van Haaften, Gij, Brancati, Francesco, Hoischen, Alexander, Huang, Haigen, Valkanas, Elise, Pusey, Barbara, Schanze, Denny, Venselaar, Hanka, Vulto-Van Silfhout, Anneke T., Wolfe, Lynne A., Tifft, Cynthia J., Zerfas, Patricia M., Zambruno, Giovanna, Kariminejad, Ariana, Sabbagh-Kermani, Farahnaz, Lee, Janice, Tsokos, Maria G., Lee, Chyi-Chia R., Ferraz, Victor, Da Silva, Eduarda Morgana, Stevens, Cathy A., Roche, Nathalie, Bartsch, Oliver, Farndon, Peter, Bermejo-Sanchez, Eva, Brooks, Brian P., Maduro, Valerie, Dallapiccola, Bruno, Ramos, Feliciano J., Chung, Hon-Yin Brian, Le Caignec, Cédric, Martins, Fabiana, Jacyk, Witold K., Mazzanti, Laura, Brunner, Han G., Bakkers, Jeroen, Lin, Shuo, Malicdan, May Christine V., Boerkoel, Cornelius F., Gahl, William A., De Vries, Bert B.A., Van Haelst, Mieke M., Zenker, Martin, Markello, Thomas C., Hubrecht Institute for Developmental Biology and Stem Cell Research |
| المصدر: | American Journal of Human Genetics, 97, 1, pp. 99-110 Marchegiani, S, Davis, T, Tessadori, F, van Haaften, G, Brancati, F, Hoischen, A, Huang, H, Valkanas, E, Pusey, B, Schanze, D, Venselaar, H, Vulto-van Silfhout, A T, Wolfe, L A, Tifft, C J, Zerfas, P M, Zambruno, G, Kariminejad, A, Sabbagh-Kermani, F, Lee, J, Tsokos, M G, Lee, C-C R, Ferraz, V, da Silva, E M, Stevens, C A, Roche, N, Bartsch, O, Farndon, P, Bermejo-Sanchez, E, Brooks, B P, Maduro, V, Dallapiccola, B, Ramos, F J, Chung, H-Y B, Le Caignec, C, Martins, F, Jacyk, W K, Mazzanti, L, Brunner, H G, Bakkers, J, Lin, S, Malicdan, M C V, Boerkoel, C F, Gahl, W A, de Vries, B B A, van Haelst, M M, Zenker, M & Markello, T C 2015, ' Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes ', American journal of human genetics, vol. 97, no. 1, pp. 99-110 . https://doi.org/10.1016/j.ajhg.2015.05.017Test American Journal of Human Genetics, 97, 99-110 American Journal of Human Genetics, 97(1), 99. Cell Press American journal of human genetics, 97(1), 99-110. Cell Press American Journal of Human Genetics, 97(1), 99-110. Cell Press Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Models, Molecular, Candidate gene, Hirsutism, Protein Conformation, HeLa Cell, medicine.disease_cause, Transcriptome, Twist transcription factor, Models, Genetics(clinical), Exome, Eye Abnormalities, Non-U.S. Gov't, Genetics (clinical), Zebrafish, Genetics, Mutation, Microscopy, Macrostomia, Setleis syndrome, Hypertelorism, Research Support, Non-U.S. Gov't, Hypertrichosi, Eyelid Disease, GENÉTICA, Phenotype, Eyelid Diseases, Abnormalities, Multiple, Sequence Analysis, Human, Chromatin Immunoprecipitation, Molecular Sequence Data, Mutation, Missense, Hypertrichosis, Amino Acid Sequence, Animals, Base Sequence, HeLa Cells, Humans, Electron, Missense, Repressor Proteins, DNA, Skin Abnormalities, Twist Transcription Factor, Molecular, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Biology, Research Support, Article, Frameshift mutation, Genetic, Ablepharon macrostomia syndrome, Skin Abnormalitie, medicine, Journal Article, Abnormalities, Multiple, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Animal, Twist-Related Protein 1, Sequence Analysis, DNA, Repressor Protein, medicine.disease, Eye Abnormalitie, Microscopy, Electron, sense organs, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] |
| الوصف: | Contains fulltext : 153827.pdf (Publisher’s version ) (Open Access) Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding. |
| وصف الملف: | application/pdf; image/pdf; ELETTRONICO |
| اللغة: | English |
| تدمد: | 0002-9297 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1749856e024ae1fd6a1491db82f32077Test https://doi.org/10.1016/j.ajhg.2015.05.017Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1749856e024ae1fd6a1491db82f32077 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029297 |
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