How to cite this article: Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CMA, Smeets DFCM, Menzel C, Ullmann R, Musante L, Ropers H-H. 2008. Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt–Hopkins syndrome. Am J Med Genet Part A 146A:2053–2059.
Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt–Hopkins syndrome†
Article first published online: 14 JUL 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 146A, Issue 16, pages 2053–2059, 15 August 2008
How to Cite
Kalscheuer, V. M., Feenstra, I., Van Ravenswaaij-Arts, C. M.A., Smeets, D. F.C.M., Menzel, C., Ullmann, R., Musante, L. and Ropers, H.-H. (2008), Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt–Hopkins syndrome. Am. J. Med. Genet., 146A: 2053–2059. doi: 10.1002/ajmg.a.32419
- Issue published online: 25 JUL 2008
- Article first published online: 14 JUL 2008
- Manuscript Accepted: 13 APR 2008
- Manuscript Received: 12 JUL 2007
- National Genome Research Network. Grant Numbers: NGFN 01GR0105, 01GR0414
- Deutsche Forschungsgemeinschaft. Grant Number: SFB577
- mental retardation;
- chromosome translocation;
- Pitt–Hopkins syndrome
We have characterized a de novo balanced translocation t(18;20)(q21.1;q11.2) in a female patient with mild to moderate mental retardation (MR) and minor facial anomalies. Breakpoint-mapping by fluorescence in situ hybridization indicated that on chromosome 18, the basic helix-loop-helix transcription factor TCF4 gene is disrupted by the breakpoint. TCF4 plays a role in cell fate determination and differentiation. Only recently, mutations in this gene have been shown to result in Pitt–Hopkins syndrome (PHS), defined by severe MR, epilepsy, mild growth retardation, microcephaly, daily bouts of hyperventilation starting in infancy, and distinctive facial features with deep-set eyes, broad nasal bridge, and wide mouth with widely spaced teeth. Breakpoint mapping on the derivative chromosome 20 indicated that here the rearrangement disrupted the chromodomain helicase DNA binding protein 6 (CHD6) gene. To date, there is no indication that CHD6 is involved in disease. Our study indicates that TCF4 gene mutations are not always associated with classical PHS but can give rise to a much milder clinical phenotype. Thus, the possibility exists that more patients with a less severe encephalopathy carry a mutation in this gene. © 2008 Wiley-Liss, Inc.