Communicated by Prof. Ian McIntosh
Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome†
Article first published online: 20 FEB 2009
© 2009 Wiley-Liss, Inc.
Volume 30, Issue 4, pages 669–676, April 2009
How to Cite
de Pontual, L., Mathieu, Y., Golzio, C., Rio, M., Malan, V., Boddaert, N., Soufflet, C., Picard, C., Durandy, A., Dobbie, A., Heron, D., Isidor, B., Motte, J., Newburry-Ecob, R., Pasquier, L., Tardieu, M., Viot, G., Jaubert, F., Munnich, A., Colleaux, L., Vekemans, M., Etchevers, H., Lyonnet, S. and Amiel, J. (2009), Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. Hum. Mutat., 30: 669–676. doi: 10.1002/humu.20935
- Issue published online: 20 MAR 2009
- Article first published online: 20 FEB 2009
- Manuscript Accepted: 7 OCT 2008
- Manuscript Received: 15 JUL 2008
- Agence Nationale pour la Recherche (ANR);
- the Fondation pour la Recherche Médicale (FRM)
- mental retardation
Pitt-Hopkins syndrome is a severe congenital encephalopathy recently ascribed to de novo heterozygous TCF4 gene mutations. We report a series of 13 novel PHS cases with a TCF4 mutation and show that EEG, brain magnetic resonance imagain (MRI), and immunological investigations provide valuable additional clues to the diagnosis. We confirm a mutational hot spot in the basic domain of the E-protein. Functional studies illustrate that heterodimerisation of mutant TCF4 proteins with a tissue-specific transcription factor is less effective than that homodimerisation in a luciferase reporter assay. We also show that the TCF4 expression pattern in human embryonic development is widespread but not ubiquitous. In summary, we further delineate an underdiagnosed mental retardation syndrome, highlighting TCF4 function during development and facilitating diagnosis within the first year of life. Hum Mutat 0, 1–8, 2009. © 2009 Wiley-Liss, Inc.