Two percent of patients suspected of having Angelman syndrome have TCF4 mutations
Version of Record online: 11 FEB 2010
© 2010 John Wiley & Sons A/S
Volume 78, Issue 3, pages 282–288, September 2010
How to Cite
Takano, K., Lyons, M., Moyes, C., Jones, J. and Schwartz, C. (2010), Two percent of patients suspected of having Angelman syndrome have TCF4 mutations. Clinical Genetics, 78: 282–288. doi: 10.1111/j.1399-0004.2010.01380.x
- Issue online: 3 AUG 2010
- Version of Record online: 11 FEB 2010
- Received 13 November 2009, revised and accepted for publication 18 January 2010
- Hopkins syndrome;
Takano K, Lyons M, Moyes C, Jones J, Schwartz CE. Two percent of patients suspected of having Angelman syndrome have TCF4 mutations.
The TCF4 gene encodes a basic helix–loop–helix (bHLH) transcription factor which belongs to the family of E-proteins. E-proteins form homo- and heterodimers with other members of the HLH family and bind to the common DNA sequence called E-box. Haploinsufficiency of the TCF4 gene has been found to be associated with the Pitt–Hopkins syndrome (PTHS). PTHS is characterized by severe mental retardation, a wide mouth plus other distinctive facial features (fleshy lips, beaked nose, broad nasal bridge) and breathing abnormalities. Because of some phenotypical overlap with Angelman syndrome (AS), it has been suggested that PTHS be considered in its differential diagnosis. To explore this possibility, we screened 86 patients who were suspected of having AS. All the patients were negative for UBE3A testing, and 53 were known to be negative for methylation analysis. We identified two TCF4 mutations in this cohort. The p.S384Tfsx7 mutation lacks the bHLH domain. The p.R582P mutation lies within the bHLH domain in which seven other missense mutations have been reported. Both mutations most likely affect the critical function of the bHLH domain of the TCF4 protein. In summary, we found two TCF4 mutations in 86 patients (2%) suspected to have AS. Screening for mutations in this gene should be considered in patients who present with findings of AS but who have been negative for methylation and UBE3A testing.